TIGS is following multiple pathways to treat and cure life-threatening ‘rare genetic disorders’, which are far from rare in India
Spinal Muscular Atrophy (SMA) is a genetic disorder that affects infants. Its onset is usually at birth and life expectancy for the most severe kind of SMA, Type 1 — also the most common — is two years. Babies suffering the condition are born with floppy limbs and about 95% of them die before they can even utter their first word.
There are few drugs that can treat this disorder, and none of them are available in India. These drugs have to be imported at great cost (5-10 million for one-time use) and require special permission from the government for the same. In most cases, by the time the medication arrives the patient is either dead or so badly off that nothing can be done. To add to the problem, a general lack of understanding in the medical field of such rare genetic disorders (RGDs) means that most cases go undiagnosed, misinterpreted or wrongly treated.
The Tata Institute for Genetics and Society (TIGS) wants to address all of these issues related to RGDs. “Rare disease implies there are very few patients,” says scientist Bhagyashree Kaduskar of the RGD team. “But in India more than 90 million people have RGDs, so it’s not quite so rare. Still, the numbers are not enough for pharma companies to want to invest in creating affordable cures.”
RGDs can be found in pockets of the country where endogamy [marriage within the same community or family] is practiced. Intra-caste and intra-community marriages and consanguinity [descending from the same ancestor] can lead to genetic deficiencies within a given populace, and these may persist over generations.
There are close to 8,000 RGDs that have been identified globally and about 450 of them are known to exist in India. As a first step, TIGS is preparing a database — to be published shortly — of all known RGDs in India, and this will be accessible to medical professionals across the country.
“The database will have genetic information, symptoms and prevalence details, as also information about which gene mutation has caused a particular disorder,” says scientist Iliyas Rashid, who is working on the project. “If a doctor comes across some inexplicable symptoms, she can refer to the database and check if they match a genetic disorder.”
“We want to make an mRNA-based therapeutic platform for those with RGDs,” says scientist Rajesh Iyer from TIGS’s technology platforms team. Known as messenger-RNA, this is a molecule that contains instructions for cells to create protein. “We can use that to cure RGDs because these disorders are mostly caused by the lack of a functional protein.”
This therapeutic platform is currently in the animal-testing stage. However, strict regulations may never allow it to be tested on humans. Clinical trials usually require a sufficient number of subjects but this may be hard to find with particular kinds of genetic disorders.
“Most of these diseases are time-sensitive, in that patients are deteriorating by the day,” says Ms Kaduskar. “While we are doing animal testing, if we can convince the government that we have a solution that is not toxic and could be a cure, we might be able to fast track the process to human trials.”
The most important thing is to offer diagnostic and therapeutic options at an affordable cost and as early as possible. TIGS wants to replace the expensive drugs that have to be brought from abroad with Indian substitutes.
Existing tests can be both painful and dangerous. Senior scientist Runa Hamid works on a group of disorders that affect neurotransmitters (chemical messengers that carry messages from one nerve in the body to the next). The current test for this involves drawing fluids from the brain or the spinal cord, an invasive and delicate technique that, if it goes wrong, can lead to paralysis. Instead, Ms Hamid is trying to develop a blood-based test.
Her colleague Vasanth Thamodaran has taken it a step further by working on what he calls a disease in a dish. He says: “If you want to study an RGD that affects brain cells and it’s not possible to find patient samples, we can create it in the lab using CRISPR [a process by which a precise and desirable change can be made in the genome].” Mr Thamodaran is also working to indigenise certain components of gene therapy to make the process cheaper (gene therapies cost upwards of 1 million currently).
“The ‘national rare-diseases policy’ was published in 2021, which makes it relatively recent,” adds scientist Gayatri Iyer. “Earlier, patients had to file a public interest litigation in court to request the government to release funds for treatment. Even then the highest that a patient could receive was 5 million, which wasn’t always enough.” Most patients give up on following through with treatment because it is so tedious.
The RGD team is certain about one objective: it wants to develop platforms and diagnostics that can be multiplexed to provide solutions for many kinds of disorders, not just a specific one. The proposed mRNA platform will do exactly that. “We don’t want to tackle it one disease at a time,” says Mr Iyer.