The RECODE-DCM initiative calls upon the global community of healthcare professionals working with Degenerative Cervical Myelopathy (DCM), and individuals living with DCM, to come together to solve the Top 10 Research Priorities — 10 critical questions that are relevant to the whole community. In this blog focusing on Research Priority 7: Novel Therapies, we will hear about the work of Dr Ayush Sharma, a spine surgeon from Mumbai, India.
We welcome comments from our community on our RECODE-DCM blog posts. Please share your perspectives by emailing recode@myelopathy.org — we’re listening!
Currently, medical and regenerative therapies are in their infancies for the treatment of DCM. Halting the chemical cascade behind degeneration is an ideal target for medical therapies.
Efforts are underway to evaluate the efficacy of surgery combined with pharmacological neuroprotective drugs which maximize the potential for postoperative recovery. This is where the neuropeptide drug cerebrolysin comes into the picture, because of its neuroprotective actions. It contains 85% free amino acids and 15% biologically active low-molecular-weight peptides.
Chromatography of cerebrolysin shows 17 different amino acids, including brain-derived neurotropic factor, nerve growth factor, glial cell-derived neurotropic factor and ciliary neurotropic factor, each of which contribute to neurotropic, neuroprotective, and neuroregenerative actions.
Its mechanisms of action are suggested to be via increased efficiency of aerobic neuronal metabolism [1,2], protein synthesis [1,2], neuronal differentiation [1,2], and inhibition of lipid peroxidation [1,2], while having anti-excitotoxic [1,2], anti-apoptotic effects [1,2], and immune-active properties [1,2].
Cerebrolysin has been studied in neurodegenerative conditions including Alzheimer’s disease [3], dementia [4] and moderate to severe head injury [3,4] with promising results. There has been only one published study to date of the role of cerebrolysin in conservatively managed people with DCM [5], and none in people with DCM treated surgically. This represents an important knowledge gap relevant to Research Priority 7, Novel Therapies for DCM.
To investigate the effect of cerebrolysin in people with DCM managed surgically, we first carried out a pilot study, which showed significant improvement in hand function at one year postoperatively in the cerebrolysin group compared to the placebo group [6].
Postoperative neurological recovery was better in the cerebrolysin group, with 66.7% patients showing complete neurological recovery compared to 56.7% for placebo. Importantly, there were no major adverse reactions to the drug, thus proving its safety profile.
We then conducted a prospective randomised controlled trial to analyse the functional outcomes of people with DCM treated with cerebrolysin for 10 days (a short, economical regime) after surgery [7].
We concluded that administration of cerebrolysin for 10 days following surgical decompression for DCM results in superior mJOA score, hand function and neurological function at one year when compared to placebo. This result is very exciting for a landscape in which novel therapies could reduce the growing disease burden in the world’s ageing population. Future research should be aimed at promoting awareness and widespread use of cerebrolysin and also regulating guidelines for the same.
Join the Community
Through this blog I wish to call for more scientists to join the RECODE-DCM community to work on the Top 10 Research Priorities. Advancements in clinical decision-making, surgical techniques, and postoperative care have allowed spine surgeons to manage increasingly complex spine cases, resulting in shorter surgery duration, reduced length of hospital stay, and improved clinical outcomes. Continued teamwork is required on the part of surgeons, scientists, allied professionals, and rehabilitation specialists to take this success forward.
To join the RECODE-DCM community, please sign up here.
For more on this story, please tune in to the Myelopathy Matters podcast, to hear our conversation with Dr Sharma in the June 2023 episode.
About the Author: Dr Ayush Sharma
Hello everyone, I am Dr Ayush Sharma, Chief Spine Surgeon at Dr BR Ambedkar Memorial Hospital, Mumbai, India. My special interest is in minimally invasive spine surgery and DCM.
My research team comprises doctors Nandan Marathe, Akash Shakya and Harsh Aggarwal, with multiple residents and fellows, and we focus on newer advances in DCM. I became interested in RECODE-DCM and Myelopathy.org because of their emphasis on stimulating new research into the Top 10 Research Priorities for DCM through their annual Research Award.
References
1. Masliah E, Diez-Tejedor E (2012) The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs of Today 48 (Suppl A): 3-24. DOI: 10.1358/dot.2012.48(Suppl.A).1739716
2. Al-Mosawi AJ (2020) Clinical uses of cerebrolysin in pediatric neuropsychiatry. Science World Journal of Pharmaceutical Sciences 1 (1): 1-4. DOI: 10.47690/SWJPS.2020.1104
3. Flores G, Atzori M (2014) The potential of cerebrolysin in the treatment of schizophrenia. Pharmacology & Pharmacy 5: 691-704. DOI: 10.4236/pp.2014.57079
4. Ghaffarpasand F, Torabi S, Rasti A, Niakan MH, Aghabaklou S, Pakzad F, Beheshtian MS, Tabrizi R (2018) Effects of cerebrolysin on functional outcome of patients with traumatic brain injury: a systematic review and meta-analysis. Neuropsychiatric Disease and Treatment 15: 127-135. DOI: 10.2147/NDT.S186865
5. Allam AF, Abotakia TA, Koptan W (2018) Role of cerebrolysin in cervical spondylotic myelopathy patients: a prospective randomized study. The Spine Journal 18 (7): 1136-1142. DOI: 10.1016/j.spinee.2017.11.002.
6. Sharma A, Marathe N, Aggarwal R, Singh V, Shakya A, Kamble P, Jaiswal A, Mangale N, Rocos B (2022) Prospective Randomized Control Pilot Study to Compare the Role of Injection Cerebrolysin in Operated Cases of Degenerative Cervical Myelopathy. Spine 47 (2): E58-E63. DOI: 10.1097/BRS.0000000000004131.
7. Sharma A, Agrawal H, Naseem A, Marathe N, Gajbhiye K, Subramanian S, Rocos B (2023) Prospective Randomized Control Trial to Compare the Role of Injection Cerebrolysin for 10 Days Duration Against Placebo in Operated Cases of Degenerative Cervical Myelopathy. Spine 48 (5): 295-300. DOI: 10.1097/BRS.0000000000004542.