Spinal muscular atrophy (SMA) is a debilitating genetic disease that affects the motor neurons of the spinal cord that control voluntary muscle movements. SMA is characterised by a progressive muscle weakness in the legs, arms, neck and head. Over time, the muscles responsible for swallowing and breathing may also become affected. Early diagnosis of SMA significantly increases patients’ chances of a better outcome. However, at present, genetic screening for SMA is not widely distributed, primarily due to its high cost. The project of the GenomeX team – one of the finalists in the ‘SPbU Start-up-2020’ student contest – is aimed at solving this problem.

genomex

SMA is considered ‘the most common of existing rare genetic diseases’. Before the genetic basis of SMA was understood, it had been classified into clinical subtypes based on maximum motor function achieved. Currently, however, the term SMA most frequently refers to a genetic disorder caused by mutations in the SMN1 gene. It accounts for approximately 95% of all cases.

Interestingly, out of all living creatures on this planet, this mutation was detected only in humans and bonobos, also called pygmy chimpanzees. The incidence of SMA has been estimated at 1 in 6,000–11,000 newborns, with a carrier frequency of the SMN1 gene mutation of 1 in 40–70.

Andrei Gusev is a first-year master’s student in the ‘Biology’ programme and the captain of the GenomeX team. He explained that the most severe form of SMA begins to affect infants shortly after birth. The mutated SMN1 genes do not produce enough survival motor neuron (SMN) protein. The reduced SMN protein level leads to loss of motor neurons, preventing the muscles from receiving proper signals from the brain. Without intervention within the first months of the child’s life, the disease will result in motor neuron death, which is fatal.

Today, there are two effective treatment strategies for patients with SMA. The first employs a genetically-engineered virus that enters the spinal cord and delivers fully functioning copies of the SMN1 gene directly to the patient’s motor neuron cells. The second strategy aims at modulating the SMN2 gene, a highly homologous version of SMN1. The SMN2 gene also produces SMN protein but in a very small amount. Thus, existing therapeutic strategies seek to increase the amount of functional SMN protein. Most importantly, not only are both therapies for SMA very expensive, but also their effectiveness is dependent on timely diagnosis and treatment.

Genetic screening for SMA is successfully performed in Germany, Great Britain, Taiwan and some states of the USA. At present, in Russia the SMA screening test is available only at a few medical centres in Moscow. According to Andrei Gusev, screening programmes for SMA are initiated by both local administrative entities and companies involved in SMA treatment. The captain of the GenomeX team believes that the main reason for the lack of routine screening programmes for SMA in Russia is its high cost.

Early detection and treatment of SMA is crucial since studies suggest that therapy is most effective when started in the first few months of life. Hence, screening for SMA must be included in the routine newborn screening programme. For this, the test must be affordable. And indeed, it must be reliable and accurate. It must not deliver false-positive or false-negative results. A genetic screening method for the detection of SMA developed by our team meets both requirements.

Andrei Gusev, Captain of the GenomeX team and a first-year master’s student in the ‘Biology’ programme

The SMA genetic screening kit will include: a 96-well plate for mixing reagents; filter paper for newborn blood samples collection; a reagent for DNA extraction from dried blood spots; and a carrier screening reagent for SMA. The proposed genetic screening test can be performed only in medical institutions.

Firstly, blood is collected from newborns onto special filter paper. After the blood samples are dried, they are shipped to a medical centre for testing. DNA is extracted from filter paper-bound dried blood samples. Using conventional equipment that is available at medical centres, the small amount of template DNA is increased by the polymerase chain reaction (PCR) method. PCR is a technique to make many copies of a specific DNA region in vitro. Next, an oligonucleotide (short DNA fragment), specifically synthesised for gene screening, is used as a gene-specific probe to search for the mutated gene and send a light signal upon detection. In turn, the dynamics of luminescence indicates how many mutated genes are in DNA. The pre-established luminescence curves enable determining whether an individual is a carrier, a diseased person, or has no gene mutations.

Our main scientific achievement is a unique oligonucleotide.

Andrei Gusev, Captain of the GenomeX team and a first-year master’s student in the ‘Biology’ programme

‘It differs from overseas analogues because our screening method employs Russian scientific innovations as well. This among other things enabled the development of a relatively low-cost final product. The estimated price of one screening test for SMA using our method is not expected to exceed 150 roubles,’ explains Andrei Gusev.

The idea of the start-up project was in gestation for a long time. It was initially suggested by the team’s supervisor Marianna Maretina. She is a junior research associate at D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproductology. Her research work at the Institute of Chemistry of St Petersburg University is funded by a research grant. Together with Andrei Gusev, the GemoneX team unites first-year master’s students, who are working on the project: Aleksandr  Baichikov (‘Management’) and Igor Khmelev (‘Business Administration in Digital Economy’).

The ‘SPbU Start-up’ contest is being held at the University for the fifth time. Teams that have presented best knowledge-intensive and commercially viable business models will receive monetary prizes from the Endowment Fund of St Petersburg University: 300,000 roubles for the first, 200,000 for the second, and 100,000 for the third place. Additionally, the two winning teams may be offered to establish a small innovative enterprise with the participation of St Petersburg University. Grants for their projects’ development will amount to 1,000,000 and 700,000 roubles for the first and second places respectively. For detailed information about the ‘SPbU Start-up – 2020’ student contest please visit the website of the Endowment Fund of St Petersburg University.

For product implementation, the GenomeX team plans to directly contact administrations of the Russian regions and cities, and the management of some private clinics. In addition, the project participants are considering marketing and selling their screening system overseas.