SetPoint Medical, a medtech firm based mostly in California, is growing a neuromodulatory gadget that’s meant 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 gadget is meant to be implanted on the left cervical vagus nerve in an outpatient process. It stimulates the nerve with electrical pulses. The concept is that this will 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 obtained $145 M in financing, and is at present 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 summary 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, usually leading to ache, diminished perform, bone erosion and joint deformity. The underlying reason for that is uncontrolled systemic irritation.
Remedy for RA sometimes contains biologic medicine. There have been appreciable advances within the therapy of RA over the previous 20 years, with approaches centered on biologically derived immunosuppressive medicine that focus on particular pro-inflammatory cytokines. These remedies can nonetheless have severe antagonistic results and include “black field” warnings. Roughly, 30-40% of sufferers on these biologic medicine don’t adequately reply to or are illiberal of those medicine. 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 might be much less immunosuppressive and less expensive than present standard-of-care medicine.
Medgadget: What impressed SetPoint Medical to pursue a brand new sort of therapy for inflammatory illness?
Dr. Simhambhatla: Present remedies for inflammatory illnesses act by interfering with key elements of the innate or adaptive immune response. This technique might be efficient in decreasing harm as a consequence 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 manner, 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 necessary function 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 perform, it turned clear that this can be a possible option to deal with power irritation in illnesses 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 power autoimmune illness, and we consult with this method as “neuroimmune modulation”.
Our early preclinical and scientific analysis led to the event of SetPoint’s therapy platform, which is at present 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 power of the vagus nerve to speak and modulate the immune system utilizing neurotransmitters is important to the inflammatory reflex.
The fast onset of localized immune exercise is important to take care of an an infection or harm. Additionally necessary is the coordination of a body-wide response that both recruits extra assets to the struggle or turns down irritation as soon as the fast hazard has handed. The vagus nerve innervates lots of our organs and is necessary for this unconscious, or autonomic, coordination. The vagus nerve constantly senses what’s occurring inside us, together with what immune cells are doing and the place they’re energetic.
The vagus nerve isn’t just sensory, it additionally relays instructions to the entrance line. After data relating to sensed cytokines travels to the mind there’s a reflexive sign that’s generated and travels all the way down to necessary immunocyte-resident tissues just like the spleen. The nerve releases neurotransmitters that act both immediately or not directly on immune cells by way of cell floor receptors that acknowledge these particular neurotransmitters. The affected immune cell is then reprogrammed to undertake a moderated inflammatory phenotype, by way of numerous intracellular pathways which were effectively 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 everyday “finish of irritation” program to coordinate the return to well being in illnesses characterised by power, damaging irritation.
Medgadget: Past rheumatoid arthritis, what different inflammatory illness states may benefit from neuromodulation?
Dr. Simhambhatla: The commonest power inflammatory illnesses, like RA, all share a standard characteristic; they’re characterised by tissue damaging irritation that doesn’t readily resolve however as an alternative results in extra irritation. Our neuroimmune modulation method is designed to interrupt such a vicious cycle. Different power inflammation-mediated illnesses which will profit from such a therapy embody Crohn’s illness, ulcerative colitis, psoriasis, psoriatic arthritis, and a number of sclerosis.
Medgadget: Please give us an summary 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 gadget is implanted on the left cervical vagus in an outpatient process. Physicians decide exact, computerized dosing by way of an iPad software. Sufferers recharge the gadget 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: We’ve got 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 present 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 medicine. The research will enroll as much as 250 sufferers throughout numerous 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 power medical circumstances.
Proceeds from the financing can 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…
