Scientists from Serbia Developing Cure for Spinal Muscular Atrophy with AI’s Help

The development of a considerably cheaper and more efficient medicine for mitigating the symptoms of spinal muscular atrophy (SMA) in infants is the goal of the SMAIPROTACs project, which is financed by the Science Fund of Serbia within the Prism Program. For that purpose, the fund has set aside EUR 284,781. The new drugs will be developed using artificial intelligence. Over the next three years, a team of scientists from the universities of Kragujevac and Belgrade are to develop an innovative drug which will lead to the decomposition of HDAC4 in proteasomes and thereby slow down or completely stop the degradation of muscles in patients with SMA.

In an interview with the Novosti daily, the leader of the team, Milan Mladenovic, PhD, an associate professor at the Faculty of Science in Kragujevac, says that, feeling empathy with families who are dealing with SMA, as university professors and scientists, they saw it as their obligation to contribute to the fight against that disease through their work, in the hope that, several years later, their efforts would result in drugs which alleviated the symptoms of that difficult disease. That is how a team of biochemists, geneticists and organic chemists – experts in their fields – was gathered.

– Our research concept is that we don’t chemically modify human DNA and incite the forming of SMN proteins that way (an approach which has proven to be inefficient), but to try to deactivate the proteins which surround the DNA, the so-called epigenetic proteins, and thereby indirectly influence the further development of the disease – says professor Mladenovic. – Epigenetics is a scientific discipline which is rapidly expanding and has a potentially big impact on medicine. We will also make a contribution to epigenetics through the application of artificial intelligence for the designing of epigenetic medicines, thereby following the most modern trends in chemistry, pharmacology and medicine. Eventually, the designed molecules will be chemically synthesized and pharmacologically tested, in the hope that we will develop extremely efficient drugs to fight SMA.

He points out that the existing cure is ZOLGENSMA gene therapy, whereby a part of the genetic material of a harmless adenovirus, when introduced to the human genetic material, should stimulate the regeneration of SMN proteins. Numerous vaccines against other diseases, which have been used in medicine for years, function the same way. However, the preparation of such a drug and the therapy administration process itself are very expensive, amounting to USD 2.125 million per therapy.

– As I have already indicated, the medicines that we will develop will not affect the DNA, but the proteins which surround the DNA of a baby – explains professor Mladenovic. – After browsing through scientific literature, we have determined that the SMA symptoms could be considerably, if not fully, mitigated if the activity of an epigenetic protein which is called histone deacetylase 4, abbreviated HDAC4, were fully turned off. To clarify, HDAC4 stimulates other proteins in the muscles to contribute to the dying out of the muscles in SMA. It is the way that we would turn off the activity of HDAC4 that is unique in the treatment of SMA and that hasn’t been tested so far.

Fond za nauku Republike Srbije

Univerzitet u Kragujevcu

Univerzitet u Beogradu

Vlada Republike Srbije

Prirodno matematički fakultet Kragujevac

Institut za informacione tehnologije Kragujevac

Science Fund of Serbia

University of Kragujevac

University of Belgrade

Government of the Republic of Serbia

Rare Diseases Association

Faculty of Science

Institute for Information Technologies

Milan Mladenović

Nevena Tomašević

Sanja Matić

Vladimir Savić

Milena Simić

Gordana Tasić

Predrag Jovanović

SMAIPROTACs

Prism Program

artificial intelligence

spinal muscular atrophy

cure for spinal muscular atrophy

HDAC4

PROTAC

medical drug testing

pharmaceutical industry

innovations

therapy

ZOLGENSMA

chemistry

pharmacology

medicine

experiments

immunobiology

toxicology

rare diseases

AI

clinical testing