Key takeaways from the meeting :

It was the sixth Patient Day organized by WWGM, with the purpose to provide a platform for patients to interact with GNE myopathy specialists, share their concerns with Doctors, listen to latest research directions and therapies from Scientists, learn about government initiatives in rare diseases, and gain from the experiences of other patients. The meeting was held online.


Latest from the clinicians -

Dr. Nalini (NIMHANS, Bengaluru), has been training the maximum number of neurologists aware of GNE myopathy in India. Earlier the disease used to be misdiagnosed at the clinical level, but now the diagnosis accuracy is high. Final diagnosis is by DNA test. Muscle biopsies are not normally taken. Time taken for final diagnosis is reducing. It is important to diagnose the disease early as the treatments work best in early stages. Why the disease is milder in some patients than others is not clear. The nature of DNA mutation could have an effect.

Dr. Khadilkar (Bombay Hospital, Mumbai), is the most respected neurologist of the country with keen interest in GNE myopathy. In the absence of an effective treatment, he advised patients about how best to manage the disease Balanced diet- avoid weight gain; do not overload with protein as it can affect kidney; no need for protein supplement Exercise- Motion across joints to maintain; strengthen muscles by resistance exercises; do not overdo, use 80% of strength Prescription- Vit D and B12 deficiency is common; alternative medicines be careful, only take from experienced doctors Rehabilitation at home- take care of mobility and accessibility at home Mental health- Anxiety, have strong social support network, join patient group etc.

Dr. Seena Vengalil (NIMHANS, Bengaluru), Natural History Study (NHS). She has initiated this study in November 2024 with funds from WWGM. What is NHS? Generates data about patient experience of the disease, symptoms, disease severity, progression etc. Why conduct NHS? Data is required by drug companies to test new drugs. It helps to give reliable endpoints for clinical trials to see if a drug is working. NHS for GNE myopathy has been done in various countries, but not in India. Indian patient mutations are different from abroad, so we have to collect our own data. What is done in NHS? Indian study is doing the same tests as abroad to make standard comparison. These are as below. Questionnaire- Participants have to answer some questions about which activities of upper and lower limbs they can perform, and which daily activities they can do without help. Muscle strength- Physiotherapist measures their upper limb strength with dynamometer and pinch gauge. Lower limb strength is measured by gait analysis (Gaitrite), and 6MWT MRI muscle is done to assess fat infiltration which shows muscle damage Blood and urine samples are collected and sent to TIGS for analysis. So far 25 participants recruited. Will recruit 50 total. Each participant will be called every 6 months.


Patients’ direct interaction with Dr. Seena, Dr. VY Vishnu (AIIMS, New Delhi), Dr. Soaham Desai (Sree Krishna hospital, Anand, Gujarat) :

The Doctors patiently answered all the queries and medical concerns of the patients.


Latest from the Scientists -

Dr. Rakesh Mishra (Director, Tata Institute for Genetics and Society, Bengaluru) TIGS, is devoting a lot of research effort in the area of rare genetic diseases. Dr. Mishra described some of their work. They are creating an interactive database of all Indian RD patients and studies on RDs. Patients can put their questions on the site and receive answers. TIGS is working on various therapeutic approaches- RNA based, cell-based, and small molecules. TIGS organizes ‘REDRESS’ annual meeting to bring together clinicians, scientists, industry, govt policy makers. Dr. Mishra concluded that good progress is now visible in the area of RDs. Policy makers are getting more involved. ICMR has given them a grant to open a Centre of Advanced Research (CAR) on RDs. ICMR director-general is very much interested to fund a clinical trial if they develop a drug.

Dr. Rajesh Iyer (Senior Scientist, TIGS), mRNA therapy for GNE myopathy They are developing this technology to deliver normal mRNA to the body using lipid nanoparticle (LNP) vehicle. Normal GNE mRNA will make normal GNE protein inside muscle cell. This will help the muscle cell to survive. For mRNA therapy injection has to be repeated every two weeks or so. But, unlike gene therapy, the dose to be given can be controlled. They have made special muscle-targeting LNPs to deliver mRNA to muscle. (Otherwise it goes to liver). Injected in mice and showed muscle delivery. Will now test how much GNE protein is made in mice after mRNA delivery. Have received big grant from ICMR for mRNA work with a number of RDs, including GNE myopathy (CAR-NGMD). Using this money they are making cell and animal models to test safety and efficacy of mRNA therapy.

Dr. Munia Ganguli (IGIB, New Delhi), Nonviral vector for gene delivery Advantages of nonviral vector over viral vector- 1. Will not be rejected by the body due to immune response; 2. Not single dose; can give repeated injections Many chemicals can be used to make nonviral vectors. They are using PBAE polymer-based vector. They have synthesized it and packed DNA. It is working well. After injection it should be stable in the body for some time, and deliver intact DNA inside the muscle cells. They have tested in muscle cell line and shown GNE protein expression. Will be testing in mice to show muscle delivery. Will improve polymer stability and DNA delivery to prevent delivery into liver.

Dr. Arkasubhra Ghosh (Narayana Nethralaya, Bengaluru), AAV-based gene delivery for GNE myopathy They have developed modified AAV capsid and tested it for muscle delivery using DMD model. Are ready for clinical trials for DMD. Have done initial studies with GNE Myopathy. Waiting for more funds. Have shown expression of GNE protein in mice after injection with AAV vector. Used muscle-specific promoter. Have made a world-class facility for production of clinical-grade AAV vector with DNA cargo. Has been approved by regulatory body. Problem with AAV is that body can reject it due to pre-existing antibodies. They have checked Indian population and shown low antibody levels for the AAV9 being used for muscle delivery. Are further optimizing protein expression to use less virus and reduce cost. Indian therapy may cost 30 to 100-times less than imported.

Dr. Ravi Manjithaya (JNCASR, Bengaluru), Urolithin A as a therapy to prevent mitophagy They are working on mitochondrial diseases where mitochondria are badly damaged. This leads to cell death. What are Mitochondria? They are the cell’s energy producing factory. Very important for muscle function. How can this damage be reversed? Normally the cell has a system to remove damaged mitochondria (Mitophagy). In disease condition the damage is too much and cell is not able to remove everything. If mitophagy can be increased, cell can remove damaged mitochondria and survive. Testing UROLITHIN A for this purpose. It is a cheap, food supplement, non-toxic, made in the body when we eat foods like pomegranate, certain berries etc. Showed UroA works to rescue mitochondrial health in disease model. Have tested Indian-made UroA (from NIPER, Kolkata). Works very well. Have to test in GNE disease model. Since it is safe for human use, permission for clinical trial can be obtained fast. They are also screening for more drugs that can improve mitochondrial health.


Latest from International Groups

Michela Onali (Sardinia, Italy), ProDGNE project Michela is a Patient Advocate who has worked along with scientists to write a research project and get EU government funds for it. Why should patients be involved? To make sure scientists are asking the right questions, are collaborating with the right people to get success, are talking to regulatory bodies to get early approvals etc. ProDGNE project aims to make a prodrug of ManNAc (ManNAc-6P) that is taken up by the body more efficiently than ManNAc alone. After 3 years the project is now over. Prodrug has still to be optimized. But project has achieved a lot. It has brought multinational scientists together. Some had never heard of GNEM before. They have made zebrafish GNEM model. They have identified biomarkers of disease. Other important leads are there which will help to understand disease. Have applied for funds for further work.

Dr. Paul Martin (Nationwide Children’s Hospital, Ohio, USA), Novel gene therapy for GNE myopathy Using dual vector technology, will express two genes at the same time. One is gene replacement- GNE normal gene to prevent further disease. Second is Muscle Booster- Follistatin gene to reverse previous damage and make new muscle. Follistatin inhibits Myostatin, a protein that inhibits muscle growth and prevents too much muscle production in the body. . They have made a better mouse model and tested dual vector in it. Follistatin along with GNE helped to improve muscle mass. . Now they plan to do toxicology studies and apply for clinical trial approval. Need funding.

Dr. Jin-Hong Shin (Pusan University, S. Korea), 6-sialyllactose for treatment of GNE myopathy 6SL is natural component of milk, hence not toxic. Have conducted a clinical trial to test 6SL in patients. Showed some improvement in upper limb strength. Can not see too much effect in 2-year study because of slow disease progression, and problem of not having proper placebo control. Expanding their clinical trial for more data. They are only working with Neuragene in Korea who make clinical-grade 6SL for testing in their clinical trial. Cannot say about quality of 6SL from other companies, like CA supplements.

Wakako Yoshioka (National Center for Neurology and Psychiatry, Tokyo, Japan), GNE myopathy management and treatment Wakako is a GNEM patient passionately involved in research. She gave overview of work going on in Japan. In Japan 60% patients are in the national registry, where their data is entered and updated every year. These data are very helpful to know disease progression. There is some correlation of disease severity with kind of gene mutation. D207V homozygous, common in Japan, is very mild, like our V727M. Some patients have respiratory function problem, bleeding due to thrombocytopenia, and sleep apnea. Should periodically check respiratory function, and platelet count. ACENOBEL sialic acid (SA-ER) drug is approved in Japan in 2024. Company not able to produce as much drug as demand. Many Japanese patients waiting. So not yet ready for international market.


Latest from Government of India

Dr. Monika Pahuja (ICMR, New Delhi) Efforts of ICMR for finding RD drugs ICMR is now focusing strongly on RDs A consortium has been formed, called National Consortium for R&D in Therapy for RDs (NCRDTRD) in 2021. All stakeholders- scientists, clinicians, approval policy persons, industry involved. Allocating funds for research. Right now, only a few RDs included, but will include more who approach them for funding. Lot of funding opportunities now for research in RDs. Have started ‘Mitra’ schemes to help researchers obtain approval from regulatory bodies. If you have a tested drug, ICMR can help to take it forward. Have funded 12 centres of excellence (CoEs) for RDs in various hospitals across the country, as of now. Plan to open more CoEs.