Dr. Dwi Kemaladewi has played a key role in developing a novel therapeutic approach, that has opened new treatment avenues for MDC1A patients. Her team’s work now involves improving the effectiveness and safety of this technology even further.
Dr. Kemaladewi is part of a research team that has developed a novel therapeutic strategy which resulted in a study that was the first to show reversal of progression of MDC1A in mice, by using technology called CRISPR-a.
In patients with MDC1A, a mutation in the LAMA2 gene results in a protein called laminin-211 being produced incompletely. This incomplete protein is the cause of muscle weakness and poor muscle growth in patients. Another protein, called laminin-111 is very similar to normal, complete laminin-211, and has been shown to improve muscle strength, nerve damage and life expectancy in MDC1A mice. Laminin-111 is naturally produced by the body during embryonic development, but production drastically decreases after birth. Despite not being produced anymore after birth, our DNA still contains the gene, or ‘recipe’, to make laminin-111, but it becomes silenced after birth. Dr. Kemaladewi’s CRISPR-a technology effectively re-activates the gene, or ‘recipe’, for laminin-111, allowing for the production of laminin-111 once again, even after birth.
Improving and optimising
This technology was able to increase muscle strength, activity, and life expectancy in adult MDC1A mice, providing a first proof-of-concept in 2019. The researchers are now working on further improving this technology. Efforts to make it cheaper, safer, easier to use, and more effective, increases the likelihood of CRISPR-a becoming a potential therapy for MDC1A patients. Moving forward, the researchers aim to test the updated and optimised version of CRISPR-a, in mice that suffer from a more severe form of MDC1A.
Ultimately, the researchers hope to eventually also test CRISPR-a in skin cells taken from MDC1A patients. This important experiment would show if CRISPR-a could also re-activate the laminin-111 gene in MDC1A patients’ cells. This would provide a vital proof-of-concept in human MDC1A cells, which will increase the chances of the therapy one day moving towards clinical trials.