Spinal Muscular Atrophy : From being denied school admission to reaching the portals of IIT Kanpur
This is the story of how a family dodged the severely debilitating rare disease.
Anushka, Anup and Archana Panda Where the mind is without fear and the head is held high - if one were to put faces to Rabindranath Tagore’s people, Archana Vashishta Panda, her husband Anup Panda, and daughter Anushka would come very close. And yet, there was a time when fear and hopelessness had become Archana’s constant companions. Her ten-month old baby, who was not just the apple of Archana’s motherly eye, but could charm anyone who set eyes on her, had begun to show worrying signs of an unknown disease. Although otherwise perfectly healthy and cheerful, baby Anushka was getting noticeably weaker in her lower limbs.
The Pandas were living in Vapi, Daman, where Anup was working for Asian Paints. Archana, an industrial engineer, was working as an auditor for environmental safety and industrial safety parameters. After her urban upbringing in Bengaluru, Archana was enjoying the small town pleasures of Daman. But Daman lacked specialist physicians who could diagnose the mysterious illness of Anushka. They were advised to see Dr. Udani, a top paediatric neurologist at Hinduja hospital, Mumbai. Archana remembers the date- 14th August, 2003 when after meeting Dr. Udani the realization dawned on them that Anushka could be suffering from a genetic disease. There were some indications in the family. Anup’s brother had developed muscle weakness when he was 14 years old and he had to abandon his favourite sport, football. He was examined at CMC, Vellore and the closest diagnosis was spinal muscular atrophy (SMA). However, in the absence of genetic testing at that time (in the 1980s), it was not clear whether, indeed, the symptoms originated from a genetic defect. In any case, the symptoms were mild enough that Anup’s brother could go on to complete his MBBS. He was pursuing MD in Radiology when he had to leave half way, as the disease was taking its toll and he was unable to continue.
With the suspicion of a genetic component, the Pandas were advised to go to Gangaram Hospital, New Delhi for a genetic test of SMA. It was mid-September, 2003 when Anushka’s blood sample was given for genetic testing. Just weeks later, on 29th September would be her first birthday. The young parents, instead of planning their baby’s first birthday party, went on a pilgrimage to Vaishno Devi to seek the Goddess’s blessings for their darling child.
Anushka, as a 6 month old baby
16th Oct 2003 The genetic report confirmed SMA- a progressive, severely debilitating disease with no treatment. Through the veil of grief that enveloped Archana and Anup, they could barely hear the Doctor’s soothing words- the disease was being very actively researched; some treatment may come out soon…. All they could think of was the bleak future that lay in store for their little baby, and the tears refused to stop. Through this period of profound grief, Archana’s mother and sister provided moral support and sound advice. They pointed out that Anushka was mentally very agile and responsive. In fact, she was sensitive enough to register her mother’s grief.
Tears are Nature’s way to wash off the darkness of gloom and welcome the sunshine of a new day. Soon this new day dawned for Archana and she resolved to fight SMA to give Anushka the best chance of a fulfilling life.
What is SMA?
Spinal muscular atrophy is a disease of the nerve cells called motor neurons, located in the spinal cord. These neurons send signals for muscle movement throughout the body. In their absence the muscle fibres remain unstimulated and begin to become smaller, or atrophy. The disease varies widely in severity and age of onset, and is classified accordingly. SMA-I is the most common and most severe. It starts before 6 months of age and the survival is for 8-14 months. SMA-II starts after 6 months; the baby can sit and maybe stand, but cannot walk. SMA-III starts after 18 months; the child is able to walk but begins to lose this ability by 2-17 years. Apart from mobility loss, complications in SMA include scoliosis (spine curving), shortening of muscles and tendons around joints, weakness of neck, throat and chest muscles leading to difficulty in chewing/ swallowing and breathing, with greater susceptibility to respiratory infections.
The disease is most often caused by mutations in the gene called Survival of Motor Neuron (SMN). The SMN gene is present in humans in two almost identical copies- SMN1 and SMN2. The difference is that SMN1 produces the normal SMN protein required for motor neuron function, whereas SMN2 is not able to retain one of its exons (exon 7) due to which it produces very low levels of the normal SMN protein.
What are Exons and why is Exon 7 not retained in SMN2 gene? It is important to understand this point as it is the basis for some of the current SMA treatments. A gene is made of DNA which transcribes its information into messenger RNA (mRNA). The mRNA can be considered a linear stretch of alphabets in which ‘sense’ segments (exons) alternate with ‘nonsense’ segments (introns). In order for the mRNA to deliver a message that makes sense it has to remove the nonsense segments and join the sense segments together in a process called splicing. It can be exemplified as follows. Consider a sequence of letters SPcLIutCE, in which the segments in bold are exons. As such the sequence does not make sense but when the exons are spliced together by removing the introns the word SPLICE is generated. In the SMN2 gene the exon at 7th position very often fails to join with its neighbouring exon and gets removed as if it was an intron. Now, under normal circumstances this does not matter as the normal SMN1 gene makes enough SMN protein. But SMA patients lack the normal SMN1 gene. Under these circumstances the small amount of normal SMN protein made by the SMN2 gene becomes crucial. It is seen that the SMN2 gene is present in different number of copies in different people. Those SMA patients who have only one copy of SMN2 are the most severely affected, while patients with two or more copies are less severely affected. While other factors may also be responsible for disease severity, the SMN2 copy number is an important factor as it is directly related to the amount of normal SMN protein being made in the patient. In fact, the first class of drugs to be tested for SMA were based on tweaking the SMN2 gene to retain its exon7.
Back in Daman, the early years
In summer 2010 - Anushka did not need spinal brace yet
Anushka was growing up to be an attractive, intelligent and articulate baby. At 18 months she could already sing in tune. But she could not walk, which attracted insensitive remarks from neighbours- an irritant Archana learnt to live with. It was essential to stay positive as there was much to be done. Since baby Anushka could not walk and exercise her muscles naturally, it was necessary to keep the good muscles from wasting by providing regular exercise. Archana discovered a Centre for cerebral palsy patients opened by a parent in the Daman hospital where physiotherapy and hydrotherapy were provided to children free of cost. As she started visiting it regularly with Anushka, she realized there were babies with even more severe problems than her own. At least her baby could talk and interact with others.
2006 Anushka was 3-plus, a bright little girl, and it was time to go to school. Archana and Anup were clear that their child must go to a regular school and not one for children with ‘special needs’. In this they were greatly encouraged by Anushka’s paediatrician, Dr. Chiragi, with whose recommendation Anushka got admitted to Sanskar Dham, a kindergarten school in Vapi. Dr. Chiragi also recognized Anushka’s inborn talent in music and she introduced her to very famous music Gurus in south Gujarat, Shri Shyamal Bhat & Gargi Bhat. Seeing baby Anushka’s rare ability to identify musical notes, the Gurus agreed to take such a small child under their wings. Thus, Anushka started learning Hindustani classical music at the age of 3 years and continues to learn and practice till today, through online classes.
2007 It was now time to get Anushka admitted to a regular high school. They tried to get her admitted to the best schools in Vapi but, to their horror, they were denied admission due to the physical disability. Just as they were contemplating action against this injustice, one of the very good schools, Gyan Dham agreed to admit her. And it was a decision the school had reason to be proud of. Anushka was such a brilliant student. She was regularly topping in quizzes, spelling bee, Olympiads, and generally excelling in Maths, English and Science. She was also keenly interested in drawing and painting. Due to weak hand muscles, it took her longer than usual to colour with crayons; nevertheless, she won various painting competitions as well. In fact, her overall performance was going so well that SMA barely made its presence felt in Anushka’s life. Yet, of course, the disease was progressing on its relentless course.
Scoliosis (2009) Till 4 years of age Anushka could raise herself from a sitting position. She was going through physiotherapy for 2 hours daily, and was gaining height. In 2009 when she was 6-plus the first symptoms of scoliosis (spine bending) began to appear. Daman did not have the specialist Doctors to advise them on management of scoliosis. The best Doctor for the purpose was Dr. Ashok Johari in Mumbai. But he was so busy that the earliest appointment they could get with him was after 2 years! With much persuasion they got a special appointment to meet the Doctor at 7am, for which they drove all night from Daman to Mumbai. To check the progression of scoliosis the Doctor suggested the use of a spinal brace, which she continues to use. In addition, Dr. Johari also advised that spine surgery could be done after Anushka was 13-plus, which would help her attain the normal height. Unfortunately, by the time she reached that age her lung function was below 40% and spine surgery became highly risky.
Pneumonia (2012) For some time Anushka had been developing respiratory issues with frequent bouts of cough that took very long to subside. In Vapi the Pandas had not been fore-warned about the respiratory problems associated with SMA. They learnt it the hard way when on 2nd September 2012 Anushka got her first major attack of pneumonia and needed to be hospitalized, with very low oxygen levels and high heart rate. She was immediately put on oxygen which improved the oxygen levels, but the heart rate remained high. When the heart beats too fast it does not fill up with blood sufficiently and cannot supply enough blood to the body. Consequently, it could lead to low blood pressure and heart failure. By 7th September Anushka had entered a critical phase and she would probably need a ventilator, which in Vapi was not available for a 10-year-old child. They were advised to immediately move to Lilavati hospital in Mumbai. The ambulance driver was a God-send. He manoeuvred through traffic to save every precious minute and completed the 6-hour journey in three and a half hours. By 7.30 pm Anushka was in the ICU and Doctors were trying their best all night to get her out of the critical phase. In that crucial period of the next 24 hours, all her dear ones, including Anushka’s entire school in their morning assembly, prayed for her. The brave girl emerged out of it under the able care of Dr. Ravinder Chittal and his team at Lilavati hospital. Archana narrates with extreme gratitude how Dr. Ravinder advised them to be always alert about respiratory issues that can recur in SMA. He told them to have an oxygen concentrator and oximeter always handy at home. Another valuable tip he gave them was to be sensitive to nasal flaring of the child as that could be a sign of oxygen deficiency. Once, when Archana was driving Anushka to school during exams, she noticed the nose flaring persistently. Sensing trouble she drove back straight to the local hospital and informed the school. They were gracious enough to give her a re-test later. Thus, a possible emergency was averted.
Madhubani Painting by Anushka in 2013
Move to Gurugram (2015) The Pandas realized that Vapi was simply not medically equipped to handle the emergencies that could arise due to SMA, and they needed to be in a larger city. Anup looked for a job close to Delhi, and in March 2015 they moved to Gurugram. Here, a large number of schools had ramps and lifts and were well equipped to handle disabilities. Anushka cleared the entrance test in six schools of Gurugram, and selected Sun City School which not only had ramps right up to 3rd floor, but also highly supportive Principal and teachers. By this time Anushka’s scoliosis had further advanced, and her arm muscles had also weakened. She could not lift her hand against gravity. She needed help for her hand to be placed on the desk and then she could write. The school provided Anushka an ergonomically suited desk with height adjustment, and other convenient features.
The Pandas took up rented accommodation a km away from Anushka’s school, and very close to Artemis hospital. As the winter of 2016 set in, Anushka suffered a serious bout of respiratory infection. The oxygen concentrator at home did not provide relief, and she had to be rushed to Artemis hospital at 2am in the night. When she recovered after a week in the ICU, Dr. Prabhat Maheshwari, her paediatrician at Artemis advised them to get a bi-level positive airway pressure (BPAP) machine at home. This machine is a non-invasive ventilator that raises the level of oxygen in the blood by pushing air into the lungs.
Class 10 Board exams (2018) Each critical episode that Anushka went through was a learning experience for the Pandas and they rose to the challenge keeping their morale high. Thus it was that in March 2018, Anushka was all set to appear for the class 10 Board exams with full confidence. Due to her disability she was entitled to get extra time in the exam, but she refused to avail of it. There was no need. When the results were announced in May, she had scored 97.8% marks; such a staggering feat that Anushka became a star. The house was full of media persons covering her story, and even the Prime Minister, Mr. Modi talked about her achievement in the July episode of “Mann ki baat”.
Preparing for the Joint Entrance Examination of IITs (2018) Anushka always wanted to study Science & engineering and decided to try for admission to computer engineering in one of the IITs. Knowing how highly competitive this was, her parents wanted to have a plan B in place. Accordingly, Anushka opted for PCM & Economics. She prepared for class 12 Board exams at school (Monday to Friday) and studied for IIT joint entrance exam on weekends. Being the most competitive entrance exam not just in India, but perhaps world-wide, one needed sound preparation, for which most students joined coaching classes. In April 2018 Anushka joined the FIIT-JEE coaching centre in Gurugram. There were major logistic problems. Classes were held on the first or second floors, and although there was an elevator, one had to climb 5 steps to reach it. So, Anushka in her wheel chair had to be lifted up the steps. Occasionally the elevator also did not work and she had to be lifted all the way. In addition, there were too many students in a single room, leaving no space for Anushka’s special ergonomic desk. They solved the problem by improvising a small, detachable table-top that was attached to Anushka’s wheel chair. For the next two years, every weekend at 8am Archana and Anup accompanied Anushka to her coaching class, stayed there to help her with any physical need, and left at 2.30pm when the class ended.
A critical episode (March 2019) As Anushka stepped into class 12, all seemed to be going well until she suffered another major respiratory infection. The medicines, nebulizer and equipment at home were to no avail and she had to be hospitalized at Artemis. It turned out to be influenza caused by the H1N1 strain of flu virus. In a couple of days she responded to the treatment and her oxygen levels improved. But, just as she seemed to have emerged out of the critical phase, all of a sudden she began to slip hopelessly. This happened as she was shifted from her bed to the wheel chair. Her oxygen levels began to fall dangerously. The hospital staff were providing oxygen at maximum pressure but she was not responding, and Archana was gripped with panic. Just then the physiotherapist suddenly appeared, as if from the void, and started mechanically moving Anushka’s rib cage to make it vibrate. The heavy sputum stuck in her trachea got ejected and oxygen levels started going up. A major catastrophe was thus averted. Archana learnt later that heavy sputum was a common feature of H1N1 infection. Due to poor muscle strength and weak cough in SMA, this could become life-threatening. Archana is certain that if Dr. Prabhat had not called for the Physiotherapist and if she had not reached immediately, things could have been otherwise.
The year 2019 was crucial, being at the cusp of the class 12 Board exams and IIT entrance exam. Archana was extremely cautious to protect Anushka from possible infections. Fortunately, Anushka sailed through the examinations without further incidence.
Just after JEE Advanced results and ready to go to IIT Kanpur
2020 : Into IIT Anushka performed brilliantly in her class 12 Board exams, and India Today news channel, in fact, informed them that she had topped the All India CBSE Science category. Although her first priority was IIT, as plan B she also secured admission in Economics in the top Colleges of Delhi. The IIT-JEE exam was postponed due to the covid pandemic. Finally, when exams were announced Anushka was exasperated to find that despite mentioning ‘physically challenged category’ in her application form, she was not assigned an exam centre on the ground floor and of course, they had no clue about ergonomics facility. Archana had to rush to the National Testing Agency, in Noida and the Joint Seat Allocation Authority (managed by IIT Delhi) to get the exam centre changed, and obtain permission for use of ergonomically suitable desk for Anushka, as she could not reach the computer key board from her wheelchair. Finally, she cracked the IIT entrance exam with a high-enough score to get into the computer science course at IIT-Kanpur. What an achievement!! No hurdle seems insurmountable for this iron-willed young woman, Anushka, and her dynamic parents.
Life at IIT-Kanpur With Anushka’s level of dependency it is not possible for her to stay in the hostel with other students. She has been allotted a room meant for Ph.D. scholars which is an independent unit with a bathroom and kitchenette. Archana lives with her and is her constant care-giver, helping her with the daily physiotherapy. They have a Bi-PAP machine and spirometer handy in the room.
The IIT-K campus is highly vibrant and abuzz with activity all day and night. It has very good accessibility with ramps at almost all academic places, and other common places. As coordinator of the student-run music club Anushka has organized several music extravaganzas. However, due to weak muscles she tires out easily and has to lie down every few hours to regain her energy.
Growing up with disability: social exclusion and an inaccessible world
Anushka’s own mental strength and the constant vigilance of her parents have made sure that her disability does not come in the way of her daily activities. Yet she has had her share of frustrating moments when she felt alone and helpless. Once in the Gyan Dham School at Vapi, due to some misunderstanding Anushka was left alone in the class while the other students went off to the Science lab. She needed help but could not call out to anyone. After this experience they decided to give her a loud whistle to attract attention for help. In this school there were no lifts. Being wheel-chair bound Anushka could not access the music room on the 2nd floor. As a result, she was left out of extracurricular activities even though she loved music and dance. The one day she hated the most in this School was the Annual Day as she played no part in the celebrations. It is not as though any of this was due to deliberate neglect by the School, as they had otherwise been really supportive of Anushka. Rather it is a reflection of how, even with the best intentions, our society is ill-prepared to be inclusive of disability.
For her class 10 Board exams, the centre was in a school with no lifts, and the examination room was on the second floor. While the rest of the class was seated upstairs, Anushka had to sit alone on the ground floor. Obviously, the arrangement was only for her convenience. Nevertheless, it does add to one’s feeling of isolation and despair. On the positive side, it also adds to one’s mental strength and prepares one to face challenges with serenity.
Each trip Anushka takes from Kanpur to Gurugram during vacations is another challenge. The Vande Bharat train has two coaches C1 & C14 for wheel chair users, but there is no mechanism in place to enter the coach from the railway platform. Archana has written innumerable letters to the authorities to rectify this problem, but it remains unresolved till date. Air travel is expensive, but the only way out for them. Even here they can only take Indigo airlines which has ramp access. With other airlines she has to be manually lifted up the stairs, which apart from being risky, ruins the alignment of Anushka’s scoliosis brace, leaving her in severe pain.
Fast-paced life in a highly competitive environment is not exactly conducive to form close bonds with peers, and with Anushka’s level of disability the world could easily pass her by. Fortunately, her brilliance and extrovert temperament has helped her to remain socially engaged at IIT. Yet, her closest friends and teachers with whom she maintains emotional connect are those from her early days at Gyan Dham School in Vapi.
The birth of CureSMA India
While in Daman, Archana and Anup had never met another SMA patient; neither had the Doctors put them in touch with other SMA patients in the country. They were battling it alone, and learning how to manage disease-related complications from their own experience. This was to change when one day, in 2014, Archana received a call from Alpana Sharma, a young mother whose child had been diagnosed with SMA. Alpana too was battling it alone, but she got a chance to visit USA where she found that SMA patients had a much better quality of life, and the families had come together to form a powerful patients’ group. Back home, Alpana started hunting for Indian parents of SMA children, and through social media she stumbled upon Anup and Archana. The two feisty moms got together; soon they found Moumita Ghosh in Kolkata, Srilakshmi in Hyderabad, Dr. Razeena in Kerala and a few other families, and they had a viable number to start the first SMA patients’ group in India- CureSMA India. Finding other families and exchanging notes was a great morale booster. They pooled their individual talents to put up a strong organizational structure which now has its mission to bring SMA treatments being developed abroad for our patients in India, and to make healthcare accessible and affordable to all patients.
CureSMA India makes sure that a newly diagnosed patient benefits from the collective knowledge of the SMA community. Families are advised about how to manage the disease; they are made aware of possible respiratory issues which could be life-threatening; about swallowing issues, feeding and nutrition; regular exercise through physiotherapy and hydrotherapy; and about assistive devices for mobility, breathing support, and braces to slow down the scoliosis. Management of SMA needs a multidisciplinary care team of experts in paediatrics, neurology, orthopaedics, pulmonology, nutrition, and physiotherapy. With the efforts of CureSMA such clinics are being organized for SMA patients in several cities. To make all this possible the CureSMA team is regularly in touch with Government agencies such as MoH&FW, DCGI, Niti Ayog, DoP, Ministry of Finance, GST council, Pharmaceutical companies who are into drug development for SMA, State level Health Ministry, NHM, MPs, and MLAs. They have also formed strategic collaboration with CureSMA USA & Europe and with Asia Pacific SMA groups. They have formed CureSMA SAARC group to support patients from our neighbouring countries.
Emerging treatments for SMA
The most successful treatments for SMA that have hit the market so far belong to two categories. 1) Drugs (Risdiplam, and Spinraza) that induce exon 7 retention in the SMN2 gene; 2) gene therapy drugs (Zolgensma) that deliver a normal copy of the SMN1 gene.
Risdiplam (Evrysdi) made by Genentech With the efforts of CureSMA this drug is now available in India with the approval of DCGI. It is recommended for patients two months or older, and is taken orally daily. It works by allowing the retention of exon 7 in SMN2 gene. The cost, even though cheaper than other SMA drugs, is still very high at Rs. 22 lakhs to 72 lakhs annually, depending on age and weight of the patient. It is the only SMA drug available in India at this point.
Spinraza (Nusinersen) made by Biogen It is an antisense oligo drug that induces retention of exon 7 in SMN2 gene. It is delivered intrathecally (that is into the spine at the lower back). It is approved for all ages of SMA patients. It is priced at USD 750,000 for the first year and USD 375,000 annually after that. It is not yet available in India. However, 200 patients in India have so far got this drug through Humanitarian Program with the US based NGO- Direct Relief. CureSMA India has been instrumental in getting this and expanding the program to more hospitals across India, to avoid long distance travel for patients and parents.
Zolgensma made by Novartis It is a gene therapy drug that delivers a normal copy of SMN1 gene into the patient, either by intravenous or intrathecal routes. It is given in a single dose to children under two years. When it was approved by USFDA in May 2019, it earned the dubious distinction of being the most expensive drug ever, priced at USD 2.1 million. In India it has been given to a few patients under the Global Managed Access Program.
Anushka on IIT Kanpur campus
What the Doctor at Gangaram hospital had told Archana in 2003 was certainly true. Amongst rare genetic diseases SMA is one of the more extensively studied, for which multiple treatment options are already available. Although encouraging, these are still baby steps. Future generations of drugs are awaited with better efficacy and tolerability; and most importantly, at a price that is affordable to an average Indian family. Meanwhile, Anushka’s journey shows us that the disease begins to take a back seat if you take charge of the driver’s seat and steer life in the direction you love. In the words of Helen Keller, Anushka’s greatest inspiration -
“Life is either a daring adventure or nothing”