Interview – Nikos Tapinos


Interview – Nikos Tapinos | Associate Professor of Neurosurgery, The Warren Albert Medical School of Brown University, Director of Molecular Neuroscience  &  Neuro Oncology Laboratory

New drugs are not available worldwide, which creates a societal discrimination

Since my lab is involved in the development of new therapeutics for brain cancer, I know first hand the tremendous expenses that we need to sustain in order to eventually move a product passed FDA approval and into the clinic.

Συνέντευξη: Κοσμάς Ζακυνθινός

Dr. Tapinos, lately, there are major scientific discoveries in the therapeutic front which relate to diseases impacting the nervous system. Do you believe that we are on the verge of the discovery of new medicines which actually cure the disease, as opposed to just slow down its evolution?

This is a somewhat general question since a lot of diseases can impact the nervous system. In most fronts, major scientific discoveries have been made during the last 5 10 years. For example, in Alzheimer’s treatment new drugs are in the pipeline for FDA approval that disrupt the underlying cause of the disease potentially slowing down or even stopping progression. Scientists believe that successful treatment for Alzheimer’s will eventually involve a combination of medications aimed at several targets, similar to current treatments for many cancers and HIV.

The important chapter “Multiple Sclerosis” is once again making front lines after the recent discoveries which set the base for the development of new clinical methods of regeneration of myelin. How encouraging is this development for patients?

In Multiple Sclerosis (MS), the progress over the last 20 years is remarkable. Just 20 years ago, we didn’t have a single drug that could specifically alter the progress of the disease. At present, disease modifying therapies (DMTs) are the best strategy to slow the course of MS. DMTs reduce the frequency and severity of relapses –or attacks and exacerbations– and the development of new lesions and slow down the progression of disability. Therapies that result in regeneration of myelin either through pharmacologic treatments or cellular therapies are currently under intense investigation and definitely are a serious reason of future hope for patients with MS.

Which is the next big ‘bet’ for scientific research conducted at Brown University and which diseases does such research focus on?

The following are some of the areas of intense research at Brown:

⦢ The BrainGate research program is focused on developing brain computer interface (BCI) technologies to restore the communication, mobility, and independence of people with neurologic disease, injury, or limb loss.

⦢ Research to map the brain circuitry underlying Alzheimer’s and other neurological disorders.

⦢ MolecularNeuro oncologyresearch to understand the molecular drivers of brain tumors and design novel therapies.

Which are the main areas of focus for research undertaken by the “Tapinos Lab” and what are the expectations/aspirations of research being conducted on Epigenetics of Glioblastoma?

We are currently focusing on the following research areas:

⦢ Role of long non coding RNAs in nerve injury response and nerve regeneration. We have identified a novel long non coding RNA that regulates the dedifferentiation of Schwann cells (glial cells of the peripheral nervous system) into repair cells that drive nerve regeneration.

⦢ We generated a non-swelling biodegradable hydrogel for controlled release of steroids that we are using to produce long term anti-inflammatory effect on constriction injuries of the sciatic nerve (lower back pain). This is a novel way to treat a very common painful condition and it helps avoid opioid dependency. We are currently at the pro clinical phase and hope to initiate a first in human clinical trial within the next three years.

⦢ We have identified cellular plasticity of human glioma stem cells as a therapeutic target to affect the course and treatment paradigm of human glioblastoma.

⦢ Glioblastoma is the most prevalent primary brain tumor and one of the most aggressive and lethal cancers. Current treatment for glioblastomas includes surgical resection of the tumor mass followed by radiation and temozolomide administration. Even with this multi therapeutic approach, tumor recurrence is inevitable. Recently, it has become evident that the marked migration properties and aggressiveness attributed to glioblastomas are driven by a population of glioma stem cells (GSCs) within the tumor mass that exhibit high migratory potential, resistance to chemotherapy and radiation and possess the ability to form secondary tumors. In addition, GSCs exhibit remarkable plasticity, are able to transition between immature and differentiated stages and can reversibly express various phenotypic markers, depending on the tumor microenvironment.

⦢ We have identified novel enhancer RNAs (eRNAs), lincRNAs, RNA modifications (m6A) that specifically regulate the glioma stem cell fate decision. Currently, several graduate students and post docs in my lab, are working to understand how each of these molecules regulates the organization of the glioma stem cell genome and how targeting of these RNAs could inhibit glioma stem cell plasticity to eventually alter the adaptability of these cells to their microenvironment cues. We are in the process of testing in animals the first RNA therapeutics against human glioma stem cells and hope to have the efficacy results in the next few months.

⦢ Discovered the mechanistic function of YKL40 in glioblastomas and produced a humanized monoclonal antibody against YKL40. We have shown that the antibody induces inhibition of tumor growth by 70% in animals. The manuscript is under review and hope to initiate first in human clinical trial within the next 3 5 years.

⦢ Developed and patented a new therapeutic modality for brain cancer, which we named “GliaTrap”. It is based on a biodegradable hydrogel that releases a potent chemoattractant for migrating tumor cells. Following surgical resection of the tumor, we fill the resection cavity with our hydrogel based GliaTrap, which releases the chemoattractant in the brain parenchyma for a regulated time. Migrating tumor cells, “sense” the chemoattractant gradient and accumulate in the close vicinity of the GliaTrap, where we can perform localized therapies to induce cytotoxicity. This novel therapy is currently being tested in animals and we hope to move to clinical trials in patients within the next 5 years.

The development of innovative cures for a several serious diseases is currently a given, particularly in the area of oncology. However, an important question is being raised globally regarding the cost of such cures. What is your view?

This is a very complicated difficult question to answer. Since my lab is involved in the development of new therapeutics for brain cancer, I know first-hand the tremendous expenses that we need to sustain in order to eventually move a product passed FDA approval and into the clinic. Just to give you an example, to move a potential therapeutic from the lab bench to Phase I clinical trials we need to spend approximately $10 million for all safety studies. Phase II and Phase III trials will add easily $100 $200 million before getting FDA approval. So, companies overprice the new drugs in order to sustain profit. Obviously, the profit margin of pharmaceutical companies is huge, and this contributes to the problem. Additionally, new drugs are not available worldwide, which creates a societal discrimination that is simply unacceptable.

Although, I understand the danger of being labeled “naïve”, my suggestion would be for humanity to reconfigure its priorities. Maybe, if we stop spending so much money to find incredible new ways to kill each other or the planet, then we may be able to put forward global policies and programs to support the discovery of new cures for cancer or any disease. These drugs will be affordable (production will be subsidized by taxpayer money), distributed equally all over the world and free for people that cannot afford even the minimum payment. Health is a universal human right and we have to start working to achieve global health. The way and the means to do all that is here today, it is just up to us to make the right decisions.

You completed the first part of your tertiary education (or college studies) in Greece. However, the scope of your research, in particular the physiology of molecular immunology led to your decision to continue your research/ career abroad. What your relationship with Greece at the moment?

My wife and kids spend two months every summer in Greece. I usually join them for 15 days or so, even though lately it is becoming difficult for me to find 15 consecutive days for vacation. When we are in Greece, we spend time with our families and friends, and we love to also visit Tinos for some days.

Professionally, could you ever consider coming back to Greece?

At present, Greece does not support high end research. Resource allocation (infrastructure, monetary support, grants, graduate programs etc.) for research purposes in Greece, remain one of the lowest in the developed world. Specifically in Life Sciences which is my area of expertise, most Greek Universities don’t have certified and competitive PhD programs for life science research, there is complete lack of international graduate and postdoctoral programs in Greece and the connection between basic science laboratories and the clinical departments is absent. In addition, technology transfer and invention disclosures and patent protection does not exist even as concepts in Greek Universities. Unfortunately, in 2020 Greek Universities are still underfunded, do not support academic excellence, they are not governed based on merit and students waste a lot of their time on political and extracurricular arguments that have no meaning for anyone in the world except the Greek political parties.

For these and many more reasons (the list is almost endless), I cannot envision a professional future for me in Greece. If a serious positive change happens during my lifetime, then I am willing to consider returning and helping the process but unfortunately, me and fellow academics in the US have almost lost all hope.

Η συνέντευξη πραγματοποιήθηκε στις 01/03/2020 | The doctor #37


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