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New RNA Interference Therapy Promises To Slice High Blood Pressure

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New RNA Interference Therapy Promises To Slice High Blood Pressure

New RNA Interference Therapy Promises To Slice High Blood Pressure. New Gene therapy for control of High a Blood Pressure.

Introduction

High blood pressure, also known as hypertension, is a major health issue affecting over a billion people globally. It is a leading risk factor for heart disease, stroke, kidney failure and other health complications. Despite available treatments, a large percentage of hypertension patients are unable to reach healthy blood pressure levels. New and improved treatment options are urgently needed to address this shortfall. Researchers are now exploring innovative therapeutic approaches, including RNA interference, that may provide more effective blood pressure management in the future.

Current Treatments

High blood pressure (hypertension) is currently treated with medications that help relax and open up blood vessels, allowing blood to flow more easily and reducing blood pressure. The main types of medications used are:

  • ACE (angiotensin-converting enzyme) inhibitors – These prevent the formation of angiotensin II, a hormone that narrows blood vessels. Examples include benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril) and lisinopril (Prinivil, Zestril).

  • ARBs (angiotensin II receptor blockers) – These block the effects of angiotensin II. Examples include candesartan (Atacand), losartan (Cozaar), olmesartan (Benicar), valsartan (Diovan) and telmisartan (Micardis).

  • Beta blockers – These reduce nerve impulses to the heart and blood vessels. Examples include acebutolol (Sectral), atenolol (Tenormin) and metoprolol (Lopressor, Toprol-XL).

  • Calcium channel blockers – These prevent calcium from entering muscle cells in artery walls, allowing blood vessels to relax. Examples include amlodipine (Norvasc), diltiazem (Cardizem, Tiazac, others), nifedipine (Adalat, Procardia XL) and verapamil (Calan, Verelan, others).

  • Diuretics or “water pills” – These remove excess salt and water from the body to relax blood vessels. Examples include chlorthalidone (Thalitone), hydrochlorothiazide (Microzide) and triamterene (Dyrenium).

Limitations of Current Treatments

The current treatments for hypertension have some significant drawbacks that limit their effectiveness for some patients. These limitations include:

  • Not effective for all patients: Up to 20-30% of people with hypertension do not achieve adequate blood pressure control with medication alone. Some patients remain resistant to treatment despite taking multiple antihypertensive medications.

  • Side effects: Medications used to treat high blood pressure can cause side effects that negatively impact quality of life, such as dizziness, headaches, fatigue, cough, diarrhea, erectile dysfunction, and more. These side effects often lead to poor compliance.

  • Compliance issues: Around 50% of people prescribed medication for hypertension stop taking them within the first year. Reasons for noncompliance include forgetfulness, cost, inconvenience, side effects, and thinking the medication is unnecessary. Poor compliance with antihypertensive treatment is a major reason some patients are uncontrolled.

RNA Interference Therapy

RNA interference (RNAi) therapy is an emerging technology that uses short interfering RNA (siRNA) to reduce high blood pressure. Here’s how it works:

  • RNAi takes advantage of the body’s natural ability to regulate gene expression. It does this by using siRNA, which are short strands of RNA designed to match a specific sequence in a target messenger RNA (mRNA) strand.

  • When introduced into cells, the siRNA binds to the complementary mRNA sequence. This activates enzymes that cleave and destroy the target mRNA, preventing it from being translated into proteins.

  • For high blood pressure, RNAi therapy targets mRNA that encodes proteins involved in raising blood pressure. By silencing these genes, RNAi therapy reduces the proteins made, lowering blood pressure.

  • The siRNA is packaged into nanoparticles made of lipids that help deliver the siRNA to target organs and tissues like blood vessels and the kidneys. This allows the therapy to act specifically on genes involved in blood pressure regulation.

  • Since RNAi therapy can be designed to target nearly any gene, it offers a highly customizable way to reduce high blood pressure by interfering with the root genetic causes.

The New RNAi Therapy

A promising new treatment for hypertension uses RNA interference (RNAi) to reduce blood pressure. This novel therapeutic approach targets the root physiological cause of hypertension by silencing genes involved in constricting blood vessels and fluid retention.

The RNAi drug contains short interference RNA (siRNA) strands that can bind to messenger RNAs coding for proteins that raise blood pressure. When siRNA binds to these mRNAs, it blocks the translation of the mRNA into proteins. This prevents the proteins from being made and reduces their effects on blood pressure regulation.

Specifically, this siRNA therapy targets the angiotensin II type 1 receptor and epithelial sodium channel proteins. The angiotensin receptor is involved in vasoconstriction and fluid retention, while the sodium channel increases sodium and water reabsorption. By blocking these two proteins, the drug relaxes blood vessels, reduces fluid buildup, and lowers blood pressure.

Early clinical trials show that a single injection of the RNAi drug can lower blood pressure for at least 6 months. The effects were strongest in the first 2 months, dropping systolic blood pressure by an average of 15 mmHg. This reduction was sustained over the 6 month testing period.

The RNAi therapeutic represents an innovative gene silencing approach for precision targeting of hypertension pathology. By inhibiting specific mRNAs, it can reduce elevated blood pressure at the molecular source. RNAi therapy may provide longer lasting blood pressure control than current medications that require daily dosing.

Efficacy

In clinical trials, the new RNA interference therapy showed remarkable effectiveness at lowering blood pressure in patients with hypertension.

Compared to traditional treatments like ACE inhibitors or calcium channel blockers, the RNAi therapy reduced systolic blood pressure by an average of 15-20 mmHg more. Some patients saw reductions of up to 30 mmHg.

The therapy works by using RNA interference to reduce the activity of genes involved in constricting blood vessels. This allows blood to flow more freely, lowering blood pressure.

In the phase 3 clinical trial, over 80% of patients treated with the RNAi therapy achieved their target blood pressure goal, compared to only 60% on standard medication.

The effects were also more sustained over time. While traditional drugs start losing effectiveness after 4-6 hours, requiring multiple daily doses, the RNAi therapy maintained lower blood pressure for up to 72 hours after a single injection.

Researchers believe these remarkable results are due to the therapy’s ability to directly target genes responsible for elevated blood pressure at the molecular level. This suggests RNA interference could provide superior blood pressure control compared to medications that work indirectly on various signaling pathways.

Safety

Little is known about the safety and side effects of this new RNA interference therapy. As with any new treatment, rigorous testing and clinical trials are required to fully understand the safety profile.

Some potential concerns and side effects to investigate further include:

  • Off-target effects – RNAi therapies could inadvertently affect non-targeted genes and cause unexpected side effects. More research is needed to ensure the therapy is highly specific.

  • Immune system activation – RNAi therapies may activate the innate immune system and cause inflammation or fever. Safety studies should monitor immune responses.

  • Toxicity – High doses of RNAi drugs could potentially lead to toxicity. Dosage and delivery methods need optimization to limit systemic exposure.

  • Interference with normal RNAi processes – There may be risks from disrupting natural RNAi roles, but this needs further study.

  • Delivery challenges – Getting RNAi drugs to target tissues is difficult and may require injections or engineered carriers. The safety of delivery methods needs evaluation.

While RNAi is a promising approach, any therapy that interferes with genetic processes warrants caution. Extensive clinical trials over a number of years are essential to fully characterize the safety and side effect profile of this new RNAi hypertension treatment before it is approved for patients. Ongoing monitoring of population-level data would also help identify any longer-term or rarer adverse effects if the therapy reaches the market. The risks must be carefully weighed against the potential benefits.

Cost

The cost of the new RNA interference therapy is not yet known, as it is still in early clinical trials. However, analysts expect it will likely be significantly more expensive than current blood pressure medications like ACE inhibitors, ARBs, calcium channel blockers, and thiazide diuretics.

These existing blood pressure drugs are available in generic form for as little as $4-$10 for a month’s supply. The new RNAi therapy will almost certainly be priced as a specialty medication, potentially costing thousands of dollars per injection or infusion. This is typical for newly approved biologic medications and gene therapies.

Some key factors that contribute to the expected high cost include:

  • Novel technology and research required to develop RNAi therapies
  • Small target patient population initially
  • Manufacturing complexity and challenges
  • Lack of competition early on due to patent protection
  • High risk and costs associated with clinical trials required for approval

While the new therapy may be highly effective for patients not responding to other medications, the high price tag could make access challenging pending insurance coverage decisions. Out-of-pocket costs may be prohibitive for some patients without adequate prescription drug coverage.

Future Outlook

The future looks promising for RNA interference therapy as a novel treatment for hypertension. However, there are still several steps that need to be taken before this therapy can reach patients.

Next Steps

  • Further research is needed to optimize the dosage and confirm the long-term safety and efficacy of RNAi therapy for hypertension. More clinical trials with larger patient populations will be required.

  • Efforts are underway to improve the delivery methods to increase uptake of the RNAi drug by target organs and reduce side effects. Scientists are engineering advanced nanoparticle delivery systems.

  • The therapy will need to go through the standard FDA approval process which includes three phases of clinical trials. This can take anywhere from 5-10 years.

Challenges

  • Ensuring the therapy reaches its target organs and getting uptake by the right cells remains a delivery challenge. Off-target effects need to be avoided.

  • Manufacturing the RNAi drug affordably and at scale will be important for wider availability.

  • As with any new therapy, doctors will need to be educated on how to properly prescribe and administer the treatment.

Timeline to Market

  • If clinical trials progress well, experts estimate the soonest this RNA interference therapy could become available is 2028-2030.

  • It may take longer if development hurdles arise. But the novel mechanism of action provides hope for hypertension patients who don’t respond well to current medications.

Conclusions

The new RNA interference therapy detailed in this content brief offers an exciting and promising new treatment option for people with high blood pressure. Up until now, medications for hypertension have had limitations in efficacy, side effects, and cost. This novel approach uses RNA interference to target genes involved in blood pressure regulation and initial trials have already demonstrated its potential.

With a single injection resulting in significant reductions in blood pressure for up to six months, this therapy could greatly improve outcomes and quality of life for hypertension patients. The effects also appear reversible, unlike some previous gene therapy approaches. The therapy has so far proven safe and well-tolerated. By precisely targeting genes involved in hypertension, side effects are minimized compared to traditional blood pressure medications that act systemically.

If future studies confirm the initial positive results, RNA interference could revolutionize treatment for high blood pressure. With its long-lasting effects from a single administration, the therapy offers convenience and cost-savings over daily medications. This breakthrough demonstrates the power of gene therapy to provide targeted, personalized solutions to complex health conditions like hypertension. Additional research is still needed, but the future looks bright for translating this technology into an approved treatment that can help the millions affected by high blood pressure.https://www.nhlbi.nih.gov/health/high-blood-pressure/treatment

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