The drug is called tegoprubart, and it represents the most significant shift in transplant immunosuppression in over a decade. Developed by Eledon Pharmaceuticals, tegoprubart is an anti-CD40L monoclonal antibody that blocks the costimulatory receptors — CD40 and CD11a — that immune cells use to coordinate attacks against transplanted organs. Unlike the calcineurin inhibitors that have dominated transplant medicine for decades, tegoprubart works through a fundamentally different mechanism, one that appears to suppress organ rejection while dramatically reducing the metabolic side effects that have long plagued transplant recipients. In a Phase 2 trial of 127 kidney transplant patients, tegoprubart matched or outperformed tacrolimus in preserving kidney function while cutting rates of new-onset diabetes, tremor, and dangerous electrolyte imbalances by staggering margins. For readers of a brain health and dementia care site, this matters more than you might think.
Organ transplant recipients face elevated risks of cognitive decline — partly from the surgeries and hospitalizations themselves, but also from the drugs they must take for life. Steroids contribute to mood disturbances, sleep disruption, and metabolic syndrome, all of which are independent risk factors for dementia. Tacrolimus, the current standard immunosuppressant, is neurotoxic enough that tremor affects one in four patients taking it. Any advance that reduces these burdens has implications not just for transplant survival, but for the long-term brain health of hundreds of thousands of people living with donor organs. This article covers how tegoprubart works and what its clinical trial results actually show, the steroid-free protocols already available at centers like Mayo Clinic, the UCLA program that aims to eliminate immunosuppressive drugs entirely, and what all of this means for cognitive health after transplant.
Table of Contents
- How Does Tegoprubart Allow Organ Transplant With Reduced Steroids and Fewer Neurological Side Effects?
- Why Steroid-Free Transplant Protocols Matter for Brain Health and Dementia Risk
- Steroid-Free Protocols Already Available at Major Transplant Centers
- From Pig Kidneys to Human Patients — Tegoprubart’s Role in Xenotransplantation
- The Push Toward Zero Immunosuppression — UCLA’s Tolerance Program
- Imlifidase and Expanding Access for High-Risk Patients
- What Comes Next — The Road to Phase 3 and Beyond
- Conclusion
- Frequently Asked Questions
How Does Tegoprubart Allow Organ Transplant With Reduced Steroids and Fewer Neurological Side Effects?
Traditional immunosuppressants like tacrolimus work by inhibiting calcineurin, an enzyme critical to T-cell activation. The problem is that calcineurin is also active in the brain and kidneys, which is why tacrolimus causes tremor in 25% of patients and gradually damages the very organ it is meant to protect. Tegoprubart sidesteps this entirely. By blocking the CD40 ligand on T-cells, it interrupts the “handshake” between immune cells that triggers a rejection cascade — without interfering with calcineurin pathways in neural tissue. The result, based on the Phase 2 BESTOW trial presented at ASN Kidney Week 2025 in Houston, is striking: tremor occurred in just 1.6% of tegoprubart patients compared to 25% on tacrolimus. The BESTOW trial randomized 127 kidney transplant recipients across 44 global sites — 63 receiving tegoprubart and 64 receiving tacrolimus — and followed them for 12 months. Mean estimated glomerular filtration rate, the standard measure of kidney function, was 69 mL/min/1.73 m² in the tegoprubart group versus 66 mL/min/1.73 m² in the tacrolimus group. Eledon has described this as the highest mean eGFR reported in larger kidney transplant trials evaluating rejection prevention.
But the safety profile is where tegoprubart really distinguishes itself. New-onset diabetes occurred in 1.6% of tegoprubart patients versus 10.9% on tacrolimus. Hyperglycemia rates were 9.5% versus 21.9%. Hyperkalemia — dangerous potassium elevation — was 11.1% versus 26.6%. Delayed graft function, where the transplanted kidney is slow to start working, dropped from 25% to 14.3%. It is worth noting a limitation: the current BESTOW protocol is not fully steroid-free. Patients still receive corticosteroids, tapered to 5 mg by day 28 post-transplant. That is significantly steroid-minimized compared to traditional regimens, but it is not steroid elimination. Whether tegoprubart can eventually support a completely steroid-free protocol is a question the planned Phase 3 trial will need to address.
Why Steroid-Free Transplant Protocols Matter for Brain Health and Dementia Risk
Corticosteroids after organ transplant are not a minor inconvenience. Chronic steroid use is associated with hippocampal atrophy, the same brain region that deteriorates early in Alzheimer’s disease. Long-term prednisone exposure disrupts the hypothalamic-pituitary-adrenal axis, elevates cortisol in ways that damage neurons, fragments sleep architecture, and contributes to depression — each of which independently raises dementia risk. For transplant recipients who may already be older adults with vascular risk factors, adding years of steroid therapy compounds an already precarious cognitive situation. The metabolic consequences are equally concerning from a brain health perspective. Post-transplant diabetes, which occurs in roughly 28% of patients on standard steroid-maintenance regimens, is one of the strongest modifiable risk factors for cognitive decline and vascular dementia.
This is not a theoretical connection. Diabetes damages small blood vessels in the brain, accelerates white matter disease, and doubles the risk of developing dementia within a decade. Any protocol that substantially lowers the incidence of post-transplant diabetes is, by extension, a neuroprotective strategy — even if that was not the original intent. However, steroid withdrawal is not appropriate for every transplant recipient. Patients with high immunological risk — those with elevated panel reactive antibodies, prior transplant failures, or certain autoimmune conditions — may still require steroid maintenance to prevent rejection. The decision to pursue a steroid-free protocol should always involve a transplant nephrologist who can weigh rejection risk against the metabolic and neurological costs of long-term corticosteroid use. Steroid avoidance is not a universal good; it is a calculated tradeoff that favors certain patient profiles over others.
Steroid-Free Protocols Already Available at Major Transplant Centers
You do not have to wait for tegoprubart to reach the market to pursue a steroid-minimized transplant. Mayo Clinic already offers steroid-free immunosuppression protocols for eligible kidney transplant recipients, and published outcomes suggest this approach is both safe and effective. One well-studied protocol uses alemtuzumab induction — a powerful antibody that depletes immune cells at the time of transplant — followed by tacrolimus monotherapy. In living donor kidney transplants using this approach, 94.4% of patients remained steroid-free from the time of surgery, and 46% were eventually maintained on spaced-dose tacrolimus monotherapy alone. The diabetes numbers tell a compelling story. In steroid-avoidance protocols, post-transplant diabetes incidence was 14.4%, compared to 27.9% in patients maintained on steroids — nearly halved.
Long-term follow-up data show that steroid avoidance remains safe and effective for up to seven years in immunologically low-risk patients, defined as those with peak panel reactive antibodies below 49%. These are not experimental results from a handful of patients; they represent mature, replicated outcomes from major academic transplant programs. The catch is that no new immunosuppressant has been FDA-approved since 2012. Every current steroid-free regimen relies on creative combinations of existing drugs — alemtuzumab, tacrolimus, mycophenolate — rather than purpose-built molecules. This means that while steroid avoidance is achievable, patients are still exposed to the neurotoxic and nephrotoxic effects of calcineurin inhibitors. Tegoprubart’s potential significance lies in the possibility of eventually replacing tacrolimus entirely, not just removing steroids from the equation.
From Pig Kidneys to Human Patients — Tegoprubart’s Role in Xenotransplantation
Tegoprubart has already been tested in one of medicine’s most ambitious frontiers: pig-to-human kidney transplantation. Tim Andrews received a genetically modified pig kidney on January 25, 2025, with tegoprubart as a key component of his immunosuppression regimen. As of reporting, Andrews has been off dialysis for more than eight months — a milestone that would have been unthinkable a few years ago. A second patient, Bill Stewart, underwent the same procedure on June 14, 2025, also using tegoprubart-based immunosuppression. The xenotransplantation application matters because it suggests tegoprubart can suppress immune responses vigorous enough to destroy an organ from another species — a far more aggressive rejection scenario than a human-to-human transplant.
If the drug can manage that level of immunological hostility, the argument for its efficacy in standard kidney transplantation becomes substantially stronger. The tradeoff, however, is that xenotransplant patients require more intensive monitoring and potentially additional immunosuppressive agents alongside tegoprubart. The pig kidney cases demonstrate the drug’s potency but cannot be directly compared to the cleaner BESTOW trial data. For the broader transplant community, xenotransplantation with tegoprubart addresses the most fundamental problem in organ transplant: there are not enough human donors. If pig-to-human transplants become routine, the combination of abundant organs and a less toxic immunosuppression regimen could transform outcomes for the hundreds of thousands of patients currently waiting on transplant lists worldwide.
The Push Toward Zero Immunosuppression — UCLA’s Tolerance Program
The most radical approach to transplant immunosuppression is to eliminate it altogether. The UCLA Tolerance Program is attempting exactly this, using donor stem cells combined with radiation therapy to retrain a recipient’s immune system to accept the transplanted kidney as self. In a Phase 1/2 trial, six patients have undergone the protocol. Three of them are now completely off all immunosuppressive drugs. The remaining patients are on reduced doses or successfully tapering. This is not a distant dream. As of January 2026, the UCLA trial opened enrollment to patients who received kidney transplants up to 20 years ago, meaning it is no longer limited to new transplant recipients.
Medicare has approved coverage for the tolerance protocol, removing one of the biggest barriers to access. If the approach scales — and that remains a significant “if” — it would eliminate not only steroids but every immunosuppressive drug, including tacrolimus and its neurotoxic effects. The limitation is obvious: six patients is not a large trial. Immune tolerance is notoriously difficult to achieve reliably, and what works in carefully selected, immunologically favorable patients may not generalize to the broader transplant population. Patients with high sensitization, prior rejections, or complex medical histories may never be candidates for tolerance induction. And the radiation component of the protocol carries its own risks. Still, the fact that three human beings are living with functioning transplanted kidneys and no immunosuppression is a proof of concept that deserves serious attention.
Imlifidase and Expanding Access for High-Risk Patients
Not every patient who needs a transplant has a cooperative immune system. Some patients develop high levels of donor-specific antibodies from prior transplants, blood transfusions, or pregnancies, making it nearly impossible to find a compatible organ. Imlifidase, a different kind of immunosuppressive agent, targets these high-risk patients by cleaving immunoglobulin G antibodies that would otherwise destroy a donor kidney within hours.
The drug is currently under FDA review and may be available as early as summer 2026. Imlifidase does not replace long-term immunosuppression — patients still need maintenance drugs after transplant. But it solves a gatekeeper problem: it allows patients who were previously considered untransplantable to receive kidneys at all. For a population that would otherwise remain on dialysis indefinitely, with all its associated cognitive decline and cardiovascular damage, that access is transformative even if the post-transplant drug regimen remains conventional.
What Comes Next — The Road to Phase 3 and Beyond
Eledon Pharmaceuticals expects FDA guidance on Phase 3 trial design for tegoprubart in the next quarter, with a goal to launch Phase 3 by the end of 2026. If that timeline holds and the larger trial confirms what BESTOW suggested, tegoprubart could become the first new transplant immunosuppressant approved in over 14 years. The implications extend well beyond nephrology.
A drug that prevents organ rejection without causing diabetes, tremor, or significant metabolic disruption would reshape how transplant teams think about long-term patient management — including cognitive outcomes. For dementia researchers and brain health advocates, the convergence of transplant immunology and neuroprotection is worth watching closely. Every reduction in post-transplant diabetes, every avoided year of steroid therapy, every patient spared tacrolimus-induced tremor represents a downstream reduction in dementia risk factors. The transplant community is not framing these advances in neurological terms, but the brain health community should be paying attention.
Conclusion
The landscape of transplant immunosuppression is shifting on multiple fronts. Tegoprubart offers a near-term alternative to tacrolimus that dramatically reduces metabolic and neurological side effects while maintaining kidney function. Steroid-free protocols using existing drugs are already available at centers like Mayo Clinic for low-risk patients. And the UCLA Tolerance Program has demonstrated that complete freedom from immunosuppressive drugs is possible, at least for a small number of carefully selected patients.
Each of these approaches addresses a different part of the problem, but they share a common direction: less toxic, more targeted immune management. For the millions of people living with transplanted organs — and for those who care for them — these developments carry real significance for long-term cognitive health. Reducing steroid exposure, avoiding tacrolimus neurotoxicity, and lowering diabetes incidence are not just transplant outcomes. They are dementia prevention strategies by another name. As tegoprubart moves toward Phase 3 and tolerance protocols expand enrollment, transplant recipients and their caregivers should discuss these emerging options with their transplant teams.
Frequently Asked Questions
Is tegoprubart FDA-approved?
No. Tegoprubart has completed a Phase 2 trial (BESTOW) and Eledon Pharmaceuticals is seeking FDA guidance on Phase 3 trial design, with the goal of launching Phase 3 by the end of 2026. It is not yet available for routine clinical use.
Can I get a steroid-free transplant right now?
Yes, for eligible patients. Centers like Mayo Clinic offer steroid-free immunosuppression protocols for kidney transplant recipients who meet specific immunological criteria, typically those with low panel reactive antibodies (below 49%). These protocols use existing approved drugs in combination.
Does tegoprubart completely eliminate the need for steroids?
Not yet. The current BESTOW trial protocol still uses corticosteroids, tapered to 5 mg by day 28 after transplant. This is significantly reduced compared to standard regimens, but it is not fully steroid-free. Whether future protocols can eliminate steroids entirely remains to be studied.
What is the UCLA Tolerance Program?
It is a clinical trial using donor stem cells and radiation therapy to retrain the immune system to accept a transplanted kidney without ongoing immunosuppressive drugs. Three of six patients in the Phase 1/2 trial are completely off all immunosuppressive medications. The program is now open to patients who received transplants up to 20 years ago, and Medicare covers the protocol.
How does post-transplant immunosuppression affect dementia risk?
Chronic steroid use is linked to hippocampal atrophy, sleep disruption, and depression — all dementia risk factors. Tacrolimus causes tremor in 25% of patients, reflecting its neurotoxic properties. Post-transplant diabetes, which occurs at rates up to 28% on standard regimens, is one of the strongest modifiable risk factors for vascular dementia and cognitive decline.
What is imlifidase?
Imlifidase is a drug under FDA review that cleaves antibodies in highly sensitized patients, allowing them to receive kidney transplants that would otherwise be rejected immediately. It may be available as early as summer 2026 and addresses access for patients who currently cannot find compatible donors.
