InterviewIssueMarch 21

Era of Personalised Transplant Treatment

Acranno Life Genomics DNA test can make life simpler for the patient as well as the doctor

It’s shocking to think that pain can be an enabler. Sometimes, the pain we feel while moving through the journey of life brings us together and can lead to wonderful things. In case of Avinash Ramani and Agragesh R, pain of seeing their loved ones suffer led to a patient-centric and technology-driven solution that is enhancing the quality-of-life of patients in India. We spoke to Agragesh to understand their journey better and to know more about their genetic and molecular diagnostic start-up, Acrannolife Genomics.

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How did you get into genetic and molecular diagnostics?

The start-up was fundamentally founded by Avinash, my Co-Founder & Chief Scientific Officer back in 2016. The idea for the company came to him while he was a PhD scholar. He identified a significant gap in transplant diagnostics and immunology space to serve the patients and the nation. At the time, I was still in B-School and Avinash was working on this research during our formative years. Our motivation to work on transplant immunology was fuelled by our personal experience with oncology and solid organ transplants in our family. We have a unique understanding of various pain a patient and their family go through.

The ultimate mission of Acrannolife is to make sure we democratise this space and enable the best possible care and technologies for everyone. We do not consider ourselves as a molecular diagnostics lab, but rather a biotech start-up building technologies and solutions for India and the world. Thus, building a self-reliant (Atma Nirbhar) India and providing a service for the nation.

 

What were the challenges in solid organ transplants and how do you help overcome these challenges?

We are looking at a key area in transplant medicine – graft rejection. We have been working on the post transplant monitoring of graft rejection since our inception. Currently, the gold-standard for post-transplant monitoring of graft rejection is throuh the conventional tissue-biopsy. This is painful, requires hospitalisation and has its own baggage of significant risks to the patients including bleeding and organ-rejection itself. Another challenge faced by the transplant teams is that the regular basic biochemical tests do not provide the real time information. The biomarkers that are sought out are slow responsive biomarkers and their quantity start showing-up (detectable value) only after a significant part of a new graft has already been damaged. Hence, we started to work on a novel technology to identify graft outcome by just a simple blood test that can tell the transplant team much before any scan or a biochemical test how the graft is working.

Tell us about your genetic tests for organ donors and recipients.

Our flagship service is a molecular assay, a blood test of sorts, which measures the DNA of the donor organ and allows us to analyse the graft condition from day one. This innovative, patent applied Trunome molecular assay identifies the graft rejection in a transplanted organ, quite early-on without the need of a biopsy.

Trunome is based on monitoring levels of DNA derived from the donor organ, circulating in the bloodstream of the transplant recipient, along with other markers in the DNA. We have also built a large database of certain genotypes to enable a few more innovations in this space for identifying sensitised patients much quicker. In addition, we also provide all types of basic pharmacogenomics tests such as for Tacrolimus or Warfarin for better, personalised medical management of transplant patients.

How can genetic testing help optimise immunosuppressant for transplant recipients?

Imunosuppressants are a big part of any recipient’s life. Most of their concerns are regarding how many medicines to take and how much. We looked at this paradigm and tried to find a better solution to the problem. Everyone has a different body makeup and varying lifestyle habits and all of these factors play a key role in a person’s response to a life-saving post-transplant immunosuppressant regime. Pharmacogenomics gives us the understanding of how the patient would metabolise or respond to a particular drug. We can now tell if the patient isa fast, slow or a normal metaboliser or a positive, neutral or a negative responder for a particular drug regime. Excess dosage of this very lifesaving immunosuppressant regime, if prescribed to a slow drug metabolizer will create toxicity in their body. While an insufficient dosage regime to a rapid metaboliser will cause the immunological rejection of the transplanted graft. Hence, an optimal balance of immunosuppressant dosages needs to be maintained in the management of transplant graft survival.

Another area of concern is that the long-term immunosuppressant regime can lead to drug resistance or non-responsiveness. Certain pharmacogenomics tests for drug resistance on long-term transplant recipients will thus help in the regulation of the immunosuppressant regime along with our proprietary Trunome molecular assay for monitoring graft rejection and other regular biochemical tests.

How do genetic tests compare with other available tests in assessing graft journey and risk management?

The available test like biopsy and blood test for biomarker levels have been around for quite some time. Both these approach have their limitations. The Trunome test is a simple blood test with quick turn-around-time. The test analyses various molecular markers from the DNA and gives a heads-up on the onset of transplant graft-rejection much earlier than existing tests. Another plus point is the cost factor. While available tests cost anywhere between Rs 30-15 thousand Trunome is much affordable. Our test is much cheaper, better, faster and most importantly safer option for the patients and the doctors to look for signs of graft injury or rejection.

Tell us about genetic testing and its benefit in early ischemic injury and DGF.

There are many molecular markers that are known to highlight the acute graft injury as well as the Delayed Graft Function (DGF). Our Trunome molecular assay can help in diagnosing acute Ischemic injury. Also, the density and the quality of the DNA in the recipient can help in quick, rapid diagnosis of ischemic graft injury. This molecular assay also pickup certain key immunological markers that can identify acute cellular rejection within 24 hours.

In addition, there are a number of molecular variants or single nucleotide polymorphisms (SNP) that play important role in our body functions including our response to drugs. Some of these SNPs are known to play a significant role in DGF. So it came naturally to us to test for these SNPs. Some of our molecular assays that identify these pathogenic SNPs can help in the diagnosis of delayed graft function as well.

Let’s talk about non-adherence to treatment in transplant recipients. How can your tests help?

Non-adherence to the life-saving immunosuppressant therapy, in post-transplant patients, is quite dangerous and can prove fatal to the patients. You need to understand that these patients have to take medicines life-long, which is very daunting and in many cases patients get discouraged either by lack of funds or due to psychological burden. When they refuse these medicines their health deteriorates and they suffer more.

Non-adherence to the post-transplant immunosuppressant medication is a problem that requires multiple interventions, including early diagnosis, proper medical management, as well as psychological counselling of patients and their immediate family members and care givers. Patients’ and their family needs to be sensitised and educated.

Organ transplant surgery alone does not completely cure their problems and that the strict-adherence to life-saving medicines as well as lifestyle changes that are to be followed post-transplant, including regular, periodic medical monitoring is key for healthy living and long-term graft survival.

Our Trunome test can predict any changes in the donor DNA in the recipient blood, which can help identify signs of rejection early on. The test can also predict changes in some key immunological markers. Periodic monitoring with our Trunome test can help identify patient’s non-adherence to medications and can lead to timely intervention like a doctor’s consult or counselling.

What do you see in the future for this technology?

We envision a better quality-of-life for all transplant patients. A simple blood test that can be done at home by patients to test for rejection and much more that will make life simpler.

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