Neuroimmune Modulation for Inflammatory Illness: Interview with Dr. Simhambhatla, President and CEO of SetPoint Medical

SetPoint Medical, a medtech firm based mostly in California, is growing a neuromodulatory machine that’s supposed to deal with rheumatoid arthritis. The overlap between the nervous and immune programs is more and more appreciated, and this expertise goals to capitalize on this to create a brand new therapy for inflammatory illness.

The neuromodulation machine is meant to be implanted on the left cervical vagus nerve in an outpatient process. It stimulates the nerve with electrical pulses. The thought is that this could act to calm inflammatory processes that contribute to rheumatoid arthritis, with out the drawbacks of immunosuppression that may come up with traditional drug remedies for the situation.

The corporate experiences that it has just lately acquired $145 M in financing, and is at the moment engaged on enrolling sufferers within the RESET-RA research, which goals to check the potential of this expertise in treating rheumatoid arthritis.

Medgadget had the chance to talk with Dr. Murthy Simhambhatla, President and CEO at SetPoint Medical, concerning the firm’s expertise and its scientific potential.   

Conn Hastings, Medgadget: Please give us an outline of rheumatoid arthritis and the way it’s handled at current.

Dr. Simhambhatla, SetPoint Medical: Greater than 1.5 million People endure from rheumatoid arthritis (RA), a situation the place the physique’s immune system assaults its personal tissue, particularly joints, typically leading to ache, diminished operate, bone erosion and joint deformity. The underlying reason for that is uncontrolled systemic irritation.

Therapy for RA usually consists of biologic medication. There have been appreciable advances within the therapy of RA over the previous 20 years, with approaches targeted on biologically derived immunosuppressive medication that concentrate on particular pro-inflammatory cytokines. These remedies can nevertheless have severe opposed results and include “black field” warnings. Roughly, 30-40% of sufferers on these biologic medication don’t adequately reply to or are illiberal of those medication. As well as, affected person compliance and therapy prices are additionally a problem. There’s a major want for brand spanking new therapeutic choices for sufferers with RA, which are much less immunosuppressive and more cost effective than present standard-of-care medication.

Medgadget: What impressed SetPoint Medical to pursue a brand new kind of therapy for inflammatory illness?

Dr. Simhambhatla: Present remedies for inflammatory ailments act by interfering with key features of the innate or adaptive immune response. This technique will be efficient in decreasing harm as a result of irritation however results in immunosuppression with dangers of extreme infections and most cancers.  

SetPoint Medical was based with the concept of dialing down irritation in a brand new method, based mostly on the invention of an innate neuro-immune reflex that helps the physique to coordinate and management systemic irritation. In a 2000 article, SetPoint’s co-founder, Dr. Kevin Tracey, printed the discovering that the vagus nerve performs an vital position in how the physique regulates irritation and importantly, that electrically stimulating the vagus nerve reduces extreme immune responses and prevents tissue harm. Observing that stimulating this advanced reflex dials down irritation by 30-70% but doesn’t shut down the protecting immunosurveillance operate, it grew to become clear that this can be a possible solution to deal with continual irritation in ailments like RA, however with out the immunosuppression related to biologics.

Since SetPoint’s founding, we’ve studied how finest to stimulate the vagus nerve to deal with continual autoimmune illness, and we seek advice from this strategy as “neuroimmune modulation”.

Our early preclinical and scientific analysis led to the event of SetPoint’s therapy platform, which is at the moment being evaluated in scientific trials for the therapy of RA. 

Medgadget: How do the nervous system and immune system work together? How does this create alternatives for therapeutic interventions?

Dr. Simhambhatla: The nervous system and the immune system advanced aspect by aspect and share the widespread language of neurotransmitters. The flexibility of the vagus nerve to speak and modulate the immune system utilizing neurotransmitters is crucial to the inflammatory reflex.

The fast onset of localized immune exercise is important to take care of an an infection or harm. Additionally vital is the coordination of a body-wide response that both recruits extra sources to the struggle or turns down irritation as soon as the instant hazard has handed. The vagus nerve innervates a lot of our organs and is vital for this unconscious, or autonomic, coordination. The vagus nerve repeatedly senses what’s taking place inside us, together with what immune cells are doing and the place they’re lively.

The vagus nerve is not only sensory, it additionally relays instructions to the entrance line. After info concerning sensed cytokines travels to the mind there’s a reflexive sign that’s generated and travels right down to vital immunocyte-resident tissues just like the spleen. The nerve releases neurotransmitters that act both straight or not directly on immune cells via cell floor receptors that acknowledge these particular neurotransmitters. The affected immune cell is then reprogrammed to undertake a moderated inflammatory phenotype, via varied intracellular pathways which have been nicely described within the literature.

This reflex is one mechanism that usually maintains immunologic homeostasis in order that the physique can each successfully struggle off infections but restrict self-damage. By electrically stimulating the vagus nerve with our exact pulse parameters, we hope to recapitulate the standard “finish of irritation” program to coordinate the return to well being in ailments characterised by continual, damaging irritation.

Medgadget: Past rheumatoid arthritis, what different inflammatory illness states may benefit from neuromodulation?

Dr. Simhambhatla: The commonest continual inflammatory ailments, like RA, all share a standard characteristic; they’re characterised by tissue damaging irritation that doesn’t readily resolve however as a substitute results in extra irritation. Our neuroimmune modulation strategy is designed to interrupt any such vicious cycle. Different continual inflammation-mediated ailments which will profit from any such therapy embody Crohn’s illness, ulcerative colitis, psoriasis, psoriatic arthritis, and a number of sclerosis.

Medgadget: Please give us an outline of your expertise and the way it works.

Dr. Simhambhatla: SetPoint Medical’s small, self-contained nerve stimulator generates exact electrical pulses utilizing an built-in circuit, telemetry {hardware} and a chargeable battery enclosed in a ceramic and titanium case. This machine is implanted on the left cervical vagus in an outpatient process. Physicians decide exact, automated dosing via an iPad software. Sufferers recharge the machine at their comfort utilizing a wi-fi charger.

Medgadget: Has the expertise progressed to scientific trials or are these within the pipeline/ongoing?

Dr. Simhambhatla: Now we have run human feasibility research in RA and Crohn’s illness, which confirmed the potential of neuroimmune modulation for the therapy of autoimmune illness. We’re at the moment enrolling sufferers in our pivotal RESET-RA research to assist a premarket approval (PMA) submission to the FDA. This can be a multicenter, double-blind, randomized, sham-controlled, research evaluating our platform for the therapy of sufferers with RA, who’re incomplete responders or illiberal to biologic medication. The research will enroll as much as 250 sufferers throughout varied U.S. research websites.

Medgadget: Congratulations on receiving $145 M in financing just lately. How does the corporate plan to spend this?

Dr. Simhambhatla: Thanks! We’re thrilled to have the assist of seasoned buyers who share our ardour for bettering outcomes for sufferers with continual medical situations.

Proceeds from the financing shall be used to finish the corporate’s ongoing RESET-RA trial, subsequent U.S. FDA regulatory submissions and early commercialization for the RA indication.

Right here’s a link to a video introducing SetPoint Medical’s investigational implant…

Hyperlink: SetPoint Medical’s homepage…