Breakthrough in Cholesterol Management: New Oral Drug Targets Genetic High Lp(a) Levels”

Lipoprotein(a), often abbreviated as Lp(a), is a unique form of cholesterol in the human body. It is considered to be a genetic variation of low-density lipoprotein (LDL) cholesterol, which is commonly referred to as “bad” cholesterol. Nearly 20 to 25 percent of people worldwide have elevated levels of Lp(a) in their bloodstream. ^(1,2)

Unlike other forms of cholesterol, such as LDL or high-density lipoprotein (HDL), which can be influenced by lifestyle changes like diet and exercise, Lp(a) levels are primarily determined by genetics. This means that conventional methods used to manage cholesterol may not effectively reduce Lp(a) levels. ⁽³⁾

While the body requires some cholesterol for vital functions, an excess of LDL cholesterol can lead to a condition called atherosclerosis. This condition involves the accumulation of cholesterol, forming plaques on the inner walls of arteries, which hinders the smooth flow of blood. ^(4,5)

Lp(a) possesses a higher propensity to stick, facilitating the buildup of plaques and potentially causing blockages in arteries. The quantity of Lp(a) in an individual’s system is largely influenced by their genetic background and ethnic heritage. For instance, individuals of African descent are more susceptible to elevated Lp(a) levels compared to other ethnic groups. ⁽⁶⁾

Having elevated Lp(a) levels can significantly heighten the risk of cardiovascular ailments, including conditions like coronary heart disease and stroke. ^(7,8,9) This underscores the importance of monitoring and managing cholesterol levels for overall heart health.

Unfortunately, as of now, there is no approved specific treatment or cure for lowering elevated Lp(a) levels. This makes it a particularly challenging form of cholesterol to manage.

However, recent breakthroughs offer hope to manage this type of cholesterol. Researchers at Monash University’s Victorian Heart Institute and Victorian Heart Hospital in Australia have conducted a groundbreaking phase 1 clinical trial, in which they have developed an experimental oral medication specifically designed to target and reduce Lp(a) levels. Remarkably, the trial demonstrated a reduction of more than half in Lp(a) levels, marking a significant advancement in the field.

This pioneering study, published in the prestigious journal JAMA, presents a promising development in the quest to address elevated Lp(a) levels, potentially opening doors to more effective treatments for individuals with this genetic variation of cholesterol. The findings offer hope for those who may be at higher risk due to elevated Lp(a) levels, bringing us one step closer to a more comprehensive approach to cholesterol management. ⁽¹⁰⁾ 

In the clinical trial mentioned above, researchers investigated muvalaplin, an experimental medication designed to lower elevated Lp(a) cholesterol levels, a known genetic risk factor for heart disease.

The prevalence of high Lp(a) levels in the population, with up to 20 percent of individuals potentially affected. Despite its association with heart disease risk, there is currently a lack of specific therapies that target Lp(a) cholesterol.

The researchers found that the manner in which muvalaplin works at a molecular level, interferes with the binding process between an LDL particle and the protein Apo(a). This effectively obstructs the formation of Lp(a) cholesterol in the liver. This mechanism, therefore, offers a promising oral treatment option for individuals with elevated Lp(a) levels. 

The study involved 114 diverse participants, evaluating muvalaplin’s safety, pharmacokinetics, and impact on Lp(a) cholesterol levels. Participants were given either a single dose, an ascending dose, or a placebo over 14 days. The results demonstrated a substantial reduction of Lp(a) levels by up to 65 percent in those who received muvalaplin.

The study reported that muvalaplin showed a favorable safety profile. Participants experienced no significant tolerability concerns or adverse effects of clinical significance. Commonly reported side effects included headache, back pain, fatigue, diarrhea, abdominal pain, and nausea.

So while the potential of muvalaplin is encouraging, the research team has stressed upon the need for more extensive clinical trials before it can become a prescribed medication. It is estimated that muvalaplin may not be available for clinical use for at least five years. 

Lowering Lp(a) levels can be challenging because they are primarily determined by genetics and do not respond significantly to lifestyle changes like diet and exercise. Due to this, lifestyle changes that typically help reduce other types of LDL cholesterol are not as effective.

Currently, the only FDA-approved treatment for lowering Lp(a) is lipoprotein apheresis, which physically removes certain lipoproteins from the blood. However, this is reserved for people with specific Lp(a) levels and additional risk factors. ^(11,12)

Scientists are also exploring PCSK9 inhibitors as a potential solution for lowering Lp(a) levels. Additionally, there are several drugs in clinical trials aimed at reducing Lp(a). ^(13,14,15)

While it is challenging, there are still some strategies that may help to some extent: 

1. Niacin (Vitamin B3): Niacin supplements have been shown to modestly lower Lp(a) levels. However, it is important to consult a healthcare provider before starting any supplementation. ⁽¹⁶⁾
2. Aspirin: Some studies suggest that aspirin may help reduce Lp(a) levels. Aspirin is often recommended for its blood-thinning properties, which can benefit overall heart health. ⁽¹⁷⁾
3. Estrogen Replacement Therapy: For postmenopausal women, estrogen replacement therapy has shown potential in reducing Lp(a) levels. However, this treatment option has to be carefully considered due to its potential risks and benefits. ⁽¹⁸⁾
4. Pharmacological Research: There are ongoing studies and research focused on developing medications specifically designed to lower Lp(a) levels. Muvalaplin, as mentioned above, is one such experimental medication showing promise.
5. Regular Monitoring: Given the genetic nature of Lp(a) levels, it is crucial for individuals with high Lp(a) to have regular check-ups with their healthcare provider. This allows for timely intervention and management of any related cardiovascular risks.
6. Maintain a Heart-Healthy Lifestyle: While lifestyle changes may not have a direct impact on Lp(a) levels, they remain important for overall cardiovascular health. This includes maintaining a balanced diet, engaging in regular physical activity, avoiding smoking, and managing other risk factors like high blood pressure and diabetes.

It is important to note that any changes or interventions should be discussed with a healthcare provider, especially when it comes to medications or supplements, as they can have individualized effects and potential interactions with other treatments. 

Apart from dealing with the genetic component of Lp(a), there are several other things you can do to keep your cholesterol levels under control. Here are some tips to help reduce high cholesterol levels: 

• Incorporate more fruits, vegetables, whole grains, and legumes into your meals.
• Choose lean proteins like poultry, fish, and plant-based alternatives.
• Limit saturated and trans fats found in fried and processed foods, as well as fatty cuts of meat.
• Opt for healthy fats like olive oil, avocados, and nuts.
• Reduce intake of sugary beverages and high-calorie snacks. 

• Include fatty fish like salmon, mackerel, and trout in your diet.
• Consider omega-3 supplements if recommended by your healthcare provider. 

• Engage in at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous-intensity activity per week.
• Incorporate strength training exercises on at least two days of the week. 

• Achieve and maintain a healthy body weight to improve cholesterol levels.

• Smoking can lower HDL (good) cholesterol and increase the risk of heart disease. 

• Moderate alcohol consumption may have some heart benefits, but excessive intake can lead to high cholesterol and other health issues. 

• Practice relaxation techniques like meditation, deep breathing, or yoga to help lower stress levels.

• Monitor your cholesterol levels through routine blood tests.
• Follow your healthcare provider’s recommendations for cholesterol management. 

• If lifestyle changes alone are insufficient, your healthcare provider may recommend cholesterol-lowering medications. 

• Include more soluble fiber-rich foods like oats, barley, fruits, and vegetables in your diet. 

• Avoid or minimize foods high in added sugars and heavily processed items, as they can contribute to high cholesterol. 

• Drink plenty of water to support overall health and metabolism. 

Remember to consult your healthcare provider before making significant changes to your diet or exercise routine, especially if you have existing health conditions or are taking medications. They can provide personalized guidance based on your specific health needs. 

The recent groundbreaking trial is sure to usher in a new era in the battle against genetic high cholesterol. The development of the first oral drug to effectively reduce Lp(a) levels by up to 65 percent over a 14-day period is a significant leap forward. This achievement not only offers hope to the millions affected by this genetic predisposition but also underscores the potential for innovative pharmaceutical interventions.

As we await further research and larger-scale trials, it is essential to recognize the collaborative efforts of researchers, medical professionals, and the pharmaceutical community in this landmark achievement. The prospect of an accessible, pill-based therapy for high Lp(a) cholesterol holds promise for a more convenient and widespread approach to cholesterol management.

While the road to widespread clinical use may be on the horizon, this breakthrough emphasizes the importance of continued research and innovation in the field of cardiovascular health. As we look to the future, the potential impact of this oral medication on reducing the risk of heart disease events remains a topic of great anticipation and hope.

References:

Also Read:

• 50 Foods to Control Cholesterol Naturally
• Eggs and Cholesterol: Do Eggs Raise Cholesterol Levels?
• Yoga Poses for Treating High Cholesterol
• Types of Cholesterol, Its Causes, Symptoms, Treatment, Hypolipidemics Drugs
• Cholesterol Basics & Ways to Control High Cholesterol
• What Happens To Your Body When You Have High Cholesterol?
• Factors That Affect Cholesterol Tests